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Blois S, Goetz BM, Mojumder A, Sullivan CS. Shedding dynamics of a DNA virus population during acute and long-term persistent infection. PLoS Pathog 2025; 21:e1013083. [PMID: 40408506 DOI: 10.1371/journal.ppat.1013083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Accepted: 05/09/2025] [Indexed: 05/25/2025] Open
Abstract
Although much is known of the molecular mechanisms of virus infection within cells, substantially less is understood about within-host infection. Such knowledge is key to understanding how viruses take up residence and transmit infectious virus, in some cases throughout the life of the host. Here, using murine polyomavirus (muPyV) as a tractable model, we monitor parallel infections of thousands of differentially barcoded viruses within a single host. In individual mice, we show that numerous viruses (>2600) establish infection and are maintained for long periods post-infection. Strikingly, a low level of many different barcodes is shed in urine at all times post-infection, with a minimum of at least 80 different barcodes present in every sample throughout months of infection. During the early acute phase, bulk shed virus genomes derive from numerous different barcodes. This is followed by long term persistent infection detectable in diverse organs. Consistent with limited productive exchange of virus genomes between organs, each displays a unique pattern of relative barcode abundance. During the persistent phase, constant low-level shedding of typically hundreds of barcodes is maintained but is overlapped with rare, punctuated shedding of high amounts of one or a few individual barcodes. In contrast to the early acute phase, these few infrequent highly shed barcodes comprise the majority of bulk shed genomes observed during late times of persistent infection, contributing to a stark decrease in bulk barcode diversity that is shed over time. These temporally shifting patterns, which are conserved across hosts, suggest that polyomaviruses balance continuous transmission potential with reservoir-driven high-level reactivation. This offers a mechanistic basis for polyomavirus ubiquity and long-term persistence, which are typical of many DNA viruses.
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Affiliation(s)
- Sylvain Blois
- Department of Molecular Biosciences, LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, Texas, United States of America
- Department of Biomedical Sciences, University of Cagliari, Monserrato, Cagliari, Italy
| | - Benjamin M Goetz
- Center for Biomedical Research Support, The University of Texas at Austin, Austin, Texas, United States of America
| | - Anik Mojumder
- Department of Molecular Biosciences, LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, Texas, United States of America
| | - Christopher S Sullivan
- Department of Molecular Biosciences, LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, Texas, United States of America
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Blois S, Goetz BM, Mojumder A, Sullivan CS. Shedding dynamics of a DNA virus population during acute and long-term persistent infection. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.31.646279. [PMID: 40236044 PMCID: PMC11996411 DOI: 10.1101/2025.03.31.646279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
Although much is known of the molecular mechanisms of virus infection within cells, substantially less is understood about within-host infection. Such knowledge is key to understanding how viruses take up residence and transmit infectious virus, in some cases throughout the life of the host. Here, using murine polyomavirus (muPyV) as a tractable model, we monitor parallel infections of thousands of differentially barcoded viruses within a single host. In individual mice, we show that numerous viruses (>2600) establish infection and are maintained for long periods post-infection. Strikingly, a low level of many different barcodes is shed in urine at all times post-infection, with a minimum of at least 80 different barcodes present in every sample throughout months of infection. During the early acute phase, bulk shed virus genomes derive from numerous different barcodes. This is followed by long term persistent infection detectable in diverse organs. Consistent with limited productive exchange of virus genomes between organs, each displays a unique pattern of relative barcode abundance. During the persistent phase, constant low-level shedding of typically hundreds of barcodes is maintained but is overlapped with rare, punctuated shedding of high amounts of one or a few individual barcodes. In contrast to the early acute phase, these few infrequent highly shed barcodes comprise the majority of bulk shed genomes observed during late times of persistent infection, contributing to a stark decrease in bulk barcode diversity that is shed over time. These temporally shifting patterns, which are conserved across hosts, suggest that polyomaviruses balance continuous transmission potential with reservoir-driven high-level reactivation. This offers a mechanistic basis for polyomavirus ubiquity and long-term persistence, which are typical of many DNA viruses. Author Summary / Importance Polyomavirus infections, mostly benign but potentially fatal for immunocompromised individuals, undergo acute and long-term persistent infections. Typically, polyomavirus-associated diseases arise due to virus infection occurring in the context of a persistently infected individual. However, little is understood regarding the mechanisms of how polyomaviruses establish, maintain, and reactivate from persistent infection. We developed a non-invasive virus shedding assay combining barcoded murine polyomavirus, massively parallel sequencing technology, and novel computational approaches to track long-term infections in mice. We expect these methods to be of use not only to the study of DNA viruses but also for understanding persitent infection of diverse microbes. The study revealed organ-specific virus reservoirs and two distinct shedding patterns: constant low-level shedding of numerous barcodes and episodic high-level shedding of few barcodes. Over time, the diversity of shed barcodes decreased substantially. These findings suggest a persistent low-level infection in multiple reservoirs, with occasional bursts of replication in a small subset of infected cells. This combination of broad reservoirs and varied shedding mechanisms may contribute to polyomavirus success in transmission and maintaining long-term infections.
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Shafqat A, Li M, Zakirullah, Liu F, Tong Y, Fan J, Fan H. A comprehensive review of research advances in the study of lactoferrin to treat viral infections. Life Sci 2025; 361:123340. [PMID: 39730037 DOI: 10.1016/j.lfs.2024.123340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 12/29/2024]
Abstract
Lactoferrin (Lf) is a naturally occurring glycoprotein known for its antiviral and antibacterial properties and is present in various physiological fluids. Numerous studies have demonstrated its antiviral effectiveness against multiple viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (IFV), herpes simplex virus (HSV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV). Lf, a vital component of the mucosal defense system, plays a crucial role in inhibiting viral infection by binding to both host cells and viral particles, such as the Hepatitis C virus (HCV). This interaction enables Lf to keep viral particles away from their target cells, emphasizing its significance as a fundamental element of mucosal defense against viral infections. Additionally, Lf has the ability to modulate cytokine expression and enhance cellular immune responses. In the innate immune system, Lf serves as a unique iron transporter and helps suppress various pathogens like bacteria, fungi, and viruses. This article summarises the potential antiviral properties of Lf against various viruses, along with its other mentioned functions. The advancement of Lf-based therapies supports the homology of food and medicine, providing a promising avenue to address viral infections and other public health challenges.
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Affiliation(s)
- Amna Shafqat
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Maochen Li
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Zakirullah
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Feitong Liu
- H&H Group, H&H Research, China Research and Innovation, Guangzhou, China.
| | - Yigang Tong
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
| | - Junfen Fan
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
| | - Huahao Fan
- School of Life Sciences, Tianjin University, Tianjin, China.
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Tang Y, Wang Z, Du D. Challenges and opportunities in research on BK virus infection after renal transplantation. Int Immunopharmacol 2024; 141:112793. [PMID: 39146777 DOI: 10.1016/j.intimp.2024.112793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 06/26/2024] [Accepted: 07/23/2024] [Indexed: 08/17/2024]
Abstract
Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges.
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Affiliation(s)
- Yukun Tang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Zipei Wang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Dunfeng Du
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
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Gerges D, Abd El-Ghany K, Hevesi Z, Aiad M, Omic H, Baumgartner C, Winnicki W, Eder M, Schmidt A, Eskandary F, Wagner L. Shedding Light on Viral Shedding: Novel Insights into Nuclear Assembly, Cytoplasmic Transformation and Extracellular Vesicle Release of the BK Virus. Int J Mol Sci 2024; 25:9130. [PMID: 39201816 PMCID: PMC11354704 DOI: 10.3390/ijms25169130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/13/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
Despite the high prevalence of BK polyomavirus (BKPyV) and the associated risk for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant (KTX) recipients, many details on viral processes such as replication, maturation, assembly and virion release from host cells have not been fully elucidated. VP1 is a polyomavirus-specific protein that is expressed in the late phase of its replicative cycle with important functions in virion assembly and infectious particle release. This study investigated the localization and time-dependent changes in the distribution of VP1-positive viral particles and their association within the spectrum of differing cell morphologies that are observed in the urine of KTX patients upon active BKPyV infection. We found highly differing recognition patterns of two anti-VP1 antibodies with respect to intracellular and extracellular VP1 localization, pointing towards independent binding sites that were seemingly associated with differing stages of virion maturation. Cells originating from single clones were stably cultured out of the urine sediment of KTX recipients with suspected BKPyVAN. The cell morphology, polyploidy, virus replication and protein production were investigated by confocal microscopy using both a monoclonal (mAb 4942) and a polyclonal rabbit anti-VP1-specific antibody (RantiVP1 Ab). Immunoblotting was performed to investigate changes in the VP1 protein. Both antibodies visualized VP1 and the mAb 4942 recognized VP1 in cytoplasmic vesicles exhibiting idiomorphic sizes when released from the cells. In contrast, the polyclonal antibody detected VP1 within the nucleus and in cytoplasm in colocalization with the endoplasmic reticulum marker CNX. At the nuclear rim, VP1 was recognized by both antibodies. Immunoblotting revealed two smaller versions of VP1 in urinary decoy cell extracts, potentially from different translation start sites as evaluated by in silico analysis. Oxford Nanopore sequencing showed integration of BKPyV DNA in chromosomes 3, 4 and 7 in one of the five tested primary cell lines which produced high viral copies throughout four passages before transcending into senescence. The different staining with two VP1-specific antibodies emphasizes the modification of VP1 during the process of virus maturation and cellular exit. The integration of BKPyV into the human genome leads to high virus production; however, this alone does not transform the cell line into a permanently cycling and indefinitely replicating one.
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Affiliation(s)
- Daniela Gerges
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Karim Abd El-Ghany
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
- Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria;
| | - Zsofia Hevesi
- Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria;
| | - Monika Aiad
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Haris Omic
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Clemens Baumgartner
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
- Division of Endocrinology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria
| | - Wolfgang Winnicki
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Michael Eder
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Alice Schmidt
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Farsad Eskandary
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
| | - Ludwig Wagner
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria; (D.G.); (K.A.E.-G.); (M.A.); (H.O.); (C.B.); (W.W.); (M.E.); (A.S.); (L.W.)
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Dekeyser M, de Goër de Herve MG, Hendel-Chavez H, Lhotte R, Scriabine I, Bargiel K, Boutin E, Herr F, Taupin JL, Taoufik Y, Durrbach A. Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus-Specific CD8 T Cell Response in Kidney Transplant Recipients. Kidney Int Rep 2024; 9:2498-2513. [PMID: 39156165 PMCID: PMC11328547 DOI: 10.1016/j.ekir.2024.04.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 04/29/2024] [Indexed: 08/20/2024] Open
Abstract
Introduction BK polyomavirus-associated nephropathy (BKPyVAN) is a significant complication in kidney transplant recipients (KTRs), associated with a higher level of plasmatic BK polyomavirus (BKPyV) replication and leading to poor graft survival. Methods We prospectively followed-up with 100 KTRs with various degrees of BKPyV reactivation (no BKPyV reactivation, BKPyV-DNAuria, BKPyV-DNAemia, and biopsy-proven BKPyVAN [bp-BKPyVAN], 25 patients per group) and evaluated BKPyV-specific T cell functionality and phenotype. Results We demonstrate that bp-BKPyVAN is associated with a loss of BKPyV-specific T cell proliferation, cytokine secretion, and cytotoxic capacities. This severe functional impairment is associated with an overexpression of lymphocyte inhibitory receptors (programmed cell death 1 [PD1], cytotoxic T lymphocyte-associated protein 4, T cell immunoreceptor with Ig and ITIM domains, and T cell immunoglobulin and mucin domain-containing-3), highlighting an exhausted-like phenotype of BKPyV-specific CD4 and CD8 T cells in bp-BKPyVAN. This T cell dysfunction is associated with low class II donor-recipient human leukocyte antigen (HLA) divergence. In contrast, in the context of higher class II donor-recipient HLA (D/R-HLA) divergence, allogeneic CD4 T cells can provide help that sustains BKPyV-specific CD8 T cell responses. In vitro, allogeneic HLA-mismatched CD4 T cells rescue BKPyV-specific CD8 T cell responses. Conclusion Our findings suggest that in KTRs, allogeneic CD4 T cells can help to maintain an effective BKPyV-specific CD8 T cell response that better controls BKPyV replication in the kidney allograft and may protect against BKPyVAN.
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Affiliation(s)
- Manon Dekeyser
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
- Department of Nephrology, Center Hospitalier Régional Universitaire d'Orléans, Orléans, France
| | | | - Houria Hendel-Chavez
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
| | - Romain Lhotte
- Laboratory of Immunology and Histocompatibility, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U976 (Team 3), Paris, France
| | - Ivan Scriabine
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
| | - Karen Bargiel
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
| | - Emmanuelle Boutin
- Unit of Clinical Research, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Creteil, France
- Paris Est Creteil University, INSERM, IMRB, CEpiA Team, Creteil, France
| | - Florence Herr
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
| | - Jean-Luc Taupin
- Laboratory of Immunology and Histocompatibility, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U976 (Team 3), Paris, France
| | - Yassine Taoufik
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
| | - Antoine Durrbach
- INSERM 1186, Gustave Roussy Institute, Villejuif, France
- Paris-Saclay University, Paris, France
- Department of Nephrology and Transplantation, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Creteil, France
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Sahragard I, Yaghobi R, Mohammadi A, Afshari A, Pakfetrat M, Hossein Karimi M, Reza Pourkarim M. Impact of BK Polyomavirus NCCR variations in post kidney transplant outcomes. Gene 2024; 913:148376. [PMID: 38490510 DOI: 10.1016/j.gene.2024.148376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 03/10/2024] [Accepted: 03/12/2024] [Indexed: 03/17/2024]
Abstract
The human BK Polyomavirus (BKPyV) is a DNA virus that is prevalent in 80 % of the population. Infection with this virus may begin in childhood, followed by asymptomatic persistence in the urinary tract. However, in immunocompromised individuals, especially kidney transplant recipients (KTRs), heightened replication of BKPyV can lead to severe complications. The genome of this virus is divided into three parts; the early and late region, and the non-coding control region (NCCR). Mutations in the NCCR can change the archetype strain to the rearranged strain, and NCCR rearrangements play a significant in virus pathogenesis. Interestingly, diverse types of NCCR block rearrangement result in significant differences in conversion potential and host cell viability in the infected cells. A correlation has been detected between increased viral replication potential and pathogenesis in BKPyV-infected KTRs with specific NCCR rearrangements. The objective of this review study was to examine the disease-causing and clinical consequences of variations in the NCCR in BKPyV-infected KTRs such as virus-associated nephropathy (BKPyVAN).
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Affiliation(s)
- Ilnaz Sahragard
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Ramin Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ali Mohammadi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Afsoon Afshari
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Pakfetrat
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mahmoud Reza Pourkarim
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute for Medical Research, Laboratory for Clinical and Epidemiological Virology, Herestraat 49 BE-3000, Leuven, Belgium
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Ferreira Menoni SM, Leon LL, de Lima RG, Lutaif ACGDB, Prates LC, Palma LMP, Costa SCB, Belangero VMS, Bonon SHA. Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome. Viruses 2024; 16:1017. [PMID: 39066180 PMCID: PMC11281385 DOI: 10.3390/v16071017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/02/2024] [Accepted: 05/03/2024] [Indexed: 07/28/2024] Open
Abstract
Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. METHODS A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. RESULTS A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133-595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. CONCLUSION viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.
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Affiliation(s)
- Silvia Mendonça Ferreira Menoni
- Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (S.M.F.M.); (L.L.L.); (R.G.d.L.); (S.C.B.C.)
| | - Lucas Lopes Leon
- Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (S.M.F.M.); (L.L.L.); (R.G.d.L.); (S.C.B.C.)
| | - Rodrigo Gonçalves de Lima
- Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (S.M.F.M.); (L.L.L.); (R.G.d.L.); (S.C.B.C.)
| | - Anna Cristina Gervásio de Brito Lutaif
- Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (A.C.G.d.B.L.); (L.C.P.); (L.M.P.P.); (V.M.S.B.)
| | - Liliane Cury Prates
- Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (A.C.G.d.B.L.); (L.C.P.); (L.M.P.P.); (V.M.S.B.)
| | - Lilian Monteiro Pereira Palma
- Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (A.C.G.d.B.L.); (L.C.P.); (L.M.P.P.); (V.M.S.B.)
| | - Sandra Cecília Botelho Costa
- Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (S.M.F.M.); (L.L.L.); (R.G.d.L.); (S.C.B.C.)
| | - Vera Maria Santoro Belangero
- Integrated Nephrology Center Unit, Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (A.C.G.d.B.L.); (L.C.P.); (L.M.P.P.); (V.M.S.B.)
| | - Sandra Helena Alves Bonon
- Laboratory of Virology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo 13083-887, Brazil; (S.M.F.M.); (L.L.L.); (R.G.d.L.); (S.C.B.C.)
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Cho A, Park S, Han A, Ha J, Park JB, Lee KW, Min S. A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients. Sci Rep 2024; 14:12855. [PMID: 38834615 PMCID: PMC11150265 DOI: 10.1038/s41598-024-60695-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/26/2024] [Indexed: 06/06/2024] Open
Abstract
BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.
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Affiliation(s)
- Ara Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Sunghae Park
- Department of Surgery, Samsung Medical Center, Seoul, South Korea
| | - Ahram Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jongwon Ha
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Seoul, South Korea
| | - Kyo Won Lee
- Department of Surgery, Samsung Medical Center, Seoul, South Korea
| | - Sangil Min
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
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10
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McAteer J, Tamma PD. Diagnosing and Managing Urinary Tract Infections in Kidney Transplant Recipients. Infect Dis Clin North Am 2024; 38:361-380. [PMID: 38729666 PMCID: PMC11090456 DOI: 10.1016/j.idc.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
Abstract
In the article, the authors review antibiotic treatment options for both acute uncomplicated UTI and complicated UTI. In addition, they review alternative regimens which are needed in the setting of drug-resistant pathogens including vancomycin-resistant Enterococcus, -extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales, and carbapenem-resistant Pseudomonas, which are encountered with more frequency.
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Affiliation(s)
- John McAteer
- Division of Pediatric Nephrology, Johns Hopkins University School of Medicine; Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Pranita D Tamma
- Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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11
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Chandraker A, Regmi A, Gohh R, Sharma A, Woodle ES, Ansari MJ, Nair V, Chen LX, Alhamad T, Norman S, Cibrik D, Singh M, Alper A, Jain D, Zaky Z, Knechtle S, Sharfuddin A, Gupta G, Lonze BE, Young JAH, Adey D, Faravardeh A, Dadhania DM, Rossi AP, Florescu D, Cardarelli F, Ma J, Gilmore S, Vasileiou S, Jindra PT, Wojciechowski D. Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. J Am Soc Nephrol 2024; 35:618-629. [PMID: 38470444 PMCID: PMC11149047 DOI: 10.1681/asn.0000000000000329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 03/05/2024] [Indexed: 03/13/2024] Open
Abstract
Key Points Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable β sequencing. Background Kidney transplant recipients with BK virus infection are at risk of developing BK virus–associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T-cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, and John Cunningham virus. Methods In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks and then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing) or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety; the secondary objective was plasma BK viral load reduction. Results Sixty-one participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events (AEs) judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3–4 AEs or serious AEs in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus–specific T cells, and the presence and persistence of posoleucel was confirmed by T-cell receptor sequencing. Conclusions Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared with placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes. Clinical Trial registry name and registration number: Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia, NCT04605484 .
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Affiliation(s)
- Anil Chandraker
- Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Division of Renal Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts
| | - Anil Regmi
- Inova Transplant Center, Falls Church, Virginia
| | | | - Akhil Sharma
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | | | | | - Vinay Nair
- Northwell Health, New Hyde Park, New York
| | - Ling-Xin Chen
- University of California Davis, Sacramento, California
| | - Tarek Alhamad
- Washington University School of Medicine at St. Louis, St. Louis, Missouri
| | | | | | | | | | | | | | | | - Asif Sharfuddin
- Indiana University School of Medicine, Indianapolis, Indiana
| | - Gaurav Gupta
- Virginia Commonwealth University, Richmond, Virginia
| | | | | | - Deborah Adey
- University of California, San Francisco, California
| | - Arman Faravardeh
- SHARP Kidney and Pancreas Transplant Center, San Diego, California
| | | | | | | | | | - Julie Ma
- AlloVir, Inc., Waltham, Massachusetts
| | | | - Spyridoula Vasileiou
- AlloVir, Inc., Waltham, Massachusetts
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas
| | - Peter T. Jindra
- Immune Evaluation Laboratory, Baylor College of Medicine, Houston, Texas
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12
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Lv Y, Liu X. Hemorrhagic cystitis induced by JC polyomavirus infection following COVID-19: a case report. BMC Urol 2024; 24:87. [PMID: 38627797 PMCID: PMC11020351 DOI: 10.1186/s12894-024-01464-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 03/24/2024] [Indexed: 04/19/2024] Open
Abstract
JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD). Subsequent metagenomic next-generation sequencing (mNGS) confirmed the infection to be caused by JCPyV type 2. Then, human immunoglobulin (PH4) for intravenous injection at a dose of 25 g QD was administered to the patient. Three days later, the hematuria resolved. This case illustrates that in the setting of compromised host immune function, JCPyV is not limited to causing central nervous system diseases but can also exhibit pathogenicity in the urinary system. Moreover, mNGS technology facilitates rapid diagnosis of infectious etiology by clinical practitioners, contributing to precise treatment for patients.
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Affiliation(s)
- Yuanjie Lv
- Department of Infection, Hospital of Traditional Chinese Medicine, Xinchang County, No.188 Shijiu Feng Road, Qixing Street, Shaoxing, 312500, China.
| | - Xiaoping Liu
- Department of Infection, Hospital of Traditional Chinese Medicine, Xinchang County, No.188 Shijiu Feng Road, Qixing Street, Shaoxing, 312500, China
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13
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Carrillo J, Del Bello A, Sallusto F, Delas A, Colombat M, Mansuy JM, Izopet J, Kamar N, Belliere J. Effect of steroid pulses in severe BK virus allograft nephropathy with extensive interstitial inflammation. Transpl Infect Dis 2024; 26:e14260. [PMID: 38547002 DOI: 10.1111/tid.14260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 02/09/2024] [Accepted: 02/12/2024] [Indexed: 04/12/2024]
Abstract
INTRODUCTION As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.
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Affiliation(s)
- Julien Carrillo
- Department of Nephrology and Organ Transplantation, Referral Centre for Rare Kidney Diseases, French Intensive Care Renal Network, University Hospital of Toulouse, Toulouse, France
| | - Arnaud Del Bello
- Department of Nephrology and Organ Transplantation, Referral Centre for Rare Kidney Diseases, French Intensive Care Renal Network, University Hospital of Toulouse, Toulouse, France
| | - Federico Sallusto
- Department of Urology and Kidney Transplantation, CHU Rangueil, Toulouse, France
| | - Audrey Delas
- Department of Pathology, University Hospital of Toulouse, University Cancer Institute of Toulouse, Toulouse, France
| | - Magali Colombat
- Department of Pathology, University Hospital of Toulouse, University Cancer Institute of Toulouse, Toulouse, France
- Université Toulouse III, Toulouse, France
| | - Jean Michel Mansuy
- Laboratory of Virology, Institut fédératif de Biologie, University Hospital of Toulouse, Toulouse, France
| | - Jacques Izopet
- Laboratory of Virology, Institut fédératif de Biologie, University Hospital of Toulouse, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Referral Centre for Rare Kidney Diseases, French Intensive Care Renal Network, University Hospital of Toulouse, Toulouse, France
- Université Toulouse III, Toulouse, France
- INSERM UMR1291-CNRS UMR5051, Toulouse, France
| | - Julie Belliere
- Department of Nephrology and Organ Transplantation, Referral Centre for Rare Kidney Diseases, French Intensive Care Renal Network, University Hospital of Toulouse, Toulouse, France
- Université Toulouse III, Toulouse, France
- INSERM U1297, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France
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14
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Lorant C, Zigmantaviciute J, Ali N, Bonnevier U, Tejde M, von Zur-Mühlen B, Eriksson BM, Bergqvist A, Westman G. The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia: a prospective study in kidney transplant recipients. BMC Infect Dis 2024; 24:245. [PMID: 38388351 PMCID: PMC10885533 DOI: 10.1186/s12879-024-09093-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 02/03/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. METHODS This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. RESULTS In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)). CONCLUSIONS Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.
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Affiliation(s)
- Camilla Lorant
- Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, SE-751 85, Uppsala, Sweden.
| | - Justina Zigmantaviciute
- Department of Medical Sciences, Clinical Microbiology, Uppsala University, Uppsala, Sweden
- Clinical Microbiology and Infection Control, Uppsala University Hospital, Uppsala, Sweden
| | - Naima Ali
- Clinical Microbiology and Infection Control, Uppsala University Hospital, Uppsala, Sweden
| | | | - Mattias Tejde
- Department of Nephrology, Falun Hospital, Falun, Sweden
| | - Bengt von Zur-Mühlen
- Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden
| | - Britt-Marie Eriksson
- Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, SE-751 85, Uppsala, Sweden
| | - Anders Bergqvist
- Department of Medical Sciences, Clinical Microbiology, Uppsala University, Uppsala, Sweden
- Clinical Microbiology and Infection Control, Uppsala University Hospital, Uppsala, Sweden
| | - Gabriel Westman
- Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, SE-751 85, Uppsala, Sweden
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15
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Anderson EM, Anderson SK. Economy of Effort or Sophisticated Programming? The Prevalence of Bidirectional Promoter Complexes in the Human Genome. Genes (Basel) 2024; 15:252. [PMID: 38397241 PMCID: PMC10887517 DOI: 10.3390/genes15020252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 02/16/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
An abundance of antisense promoters in the vicinity of the transcriptional start site of coding genes suggests that they play an important role in gene regulation. The divergent transcription of housekeeping genes by a common central promoter region allows for coordinated regulation of genes in related pathways and is also linked to higher promoter activity. However, closely positioned transcription start sites can also result in competition between overlapping promoter elements and generate a binary switch element. Furthermore, the direct competition resulting from the presence of an antisense promoter immediately downstream of the transcription start site of the gene produces an element that can exist in only one of two stable transcriptional states: sense or antisense. In this review, we summarize analyses of the prevalence of antisense transcription in higher eukaryotes and viruses, with a focus on the antisense promoters competing with the promoters of coding genes. The structures of bidirectional promoters driving the simultaneous expression of housekeeping genes are compared with examples of human bidirectional elements that have been shown to act as switches. Since many bidirectional elements contain a noncoding RNA as the divergent transcript, we describe examples of functional noncoding antisense transcripts that affect the epigenetic landscape and alter the expression of their host gene. Finally, we discuss opportunities for additional research on competing sense/antisense promoters, uncovering their potential role in programming cell differentiation.
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Affiliation(s)
- Erik M. Anderson
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA;
| | - Stephen K. Anderson
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA;
- Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
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16
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Ebrahimi N, Al Baghdadi M, Zuppan CW, Rogstad DK, Abdipour A. AIDS-Associated BK Virus Nephropathy in Native Kidneys: A Case Report and Review of the Literature. J Investig Med High Impact Case Rep 2024; 12:23247096241232202. [PMID: 38375628 PMCID: PMC10880537 DOI: 10.1177/23247096241232202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/10/2024] [Accepted: 01/28/2024] [Indexed: 02/21/2024] Open
Abstract
BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm3. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population.
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17
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Starrett GJ, Foster H, Sigel K, Liu Y, Engels EA. Brief Report: The Virome of Bladder Tumors Arising in People Living With HIV. J Acquir Immune Defic Syndr 2023; 94:337-340. [PMID: 37884054 PMCID: PMC10662940 DOI: 10.1097/qai.0000000000003283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 08/01/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND People living with HIV (PLWH) have elevated risk for developing virus-related cancers. Bladder cancer risk is not increased in PLWH but is elevated among immunosuppressed solid organ transplant recipients (SOTRs). BK polyomavirus and, to a lesser extent, other viruses have been detected in bladder cancers from SOTRs. OBJECTIVE To characterize the virome of bladder tumors in PLWH. DESIGN Retrospective case series. METHODS We sequenced DNA and RNA from archived formalin-fixed bladder tumors from PLWH. Nonhuman reads were assembled and matched to a database of known viruses. RESULTS Fifteen bladder tumors from PLWH (13 carcinomas, 2 benign tumors) were evaluated. Fourteen tumors were in men, and the median age at diagnosis was 59 years (median CD4 count 460 cells/mm3). All but 1 tumor yielded both sufficient DNA and RNA. One bladder cancer, arising in a 52-year-old man with a CD4 count of 271 cells/mm3, manifested diverse Alphatorquevirus DNA and RNA sequences. A second cancer arising in a 58-year-old male former smoker (CD4 count of 227 cells/mm3) also showed Alphatorquevirus and Gammatorquevirus DNA sequences. Neither tumor exhibited viral integration. CONCLUSIONS Alphatorqueviruses and Gammatorqueviruses are anelloviruses, which have also been detected in bladder cancers from SOTRs, but anelloviruses are common infections, and detection may simply reflect increased abundance in the setting of immunosuppression. The lack of detection of BK polyomavirus among bladder tumors from PLWH parallels the lower level of bladder cancer risk seen in PLWH compared with SOTRs, indirectly supporting a role for BK polyomavirus in causing the excess risk in SOTRs.
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Affiliation(s)
- Gabriel J. Starrett
- Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Haidn Foster
- Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Keith Sigel
- Departments of Medicine and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yuxin Liu
- Departments of Medicine and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eric A. Engels
- Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
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18
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Laine HK, Waterboer T, Syrjänen K, Grenman S, Louvanto K, Syrjänen S. IgG Seroreactivites to Viral Capsid Protein VP1 of JC and BK Polyomaviruses in Children at Early Ages with Special Reference to Parental Cofactors. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1645. [PMID: 37892308 PMCID: PMC10604957 DOI: 10.3390/children10101645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/08/2023] [Accepted: 09/19/2023] [Indexed: 10/29/2023]
Abstract
BK (BKPyV) and JC (JCPyV) polyomaviruses are widespread in humans. Transmission at an early age and the role of parents in spreading these viruses through the family are incompletely understood. Our aim was to determine the seroprevalence of BKPyV and JCPyV in infants at the age of 1, 2, 6, 12, 24, and 36 months and to assess the frequency of BKPyV and JCPyV seroconversion. A variety of maternal and paternal covariates were also tested as potential predictors of these early childhood infections. We used multiplex serology to analyze antibodies to BKPyV and JCPyV from baseline to 3-year follow-up visits. We observed that there was nearly perfect correlation in BKPyV and JCPyV serum IgG antibody levels between the mother-infant pairs during the first year of the infant's life. No correlation among BKPyV antibody titers were found in father-child pairs, whereas JCPyV antibody levels of the father and child had a significant correlation at the 2-year follow-up visit. BKPyV infection may be associated with a child's predisposition to allergy. In conclusion, after the decay of maternal antibodies, children start to develop their own immunity toward BKPyV and JCPyV, and horizontal transmission of infection in the family can occur.
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Affiliation(s)
- Hanna K. Laine
- Department of Oral and Maxillofacial Diseases, University of Helsinki, 00290 Helsinki, Finland
- Department of Oral Pathology and Radiology, Faculty of Medicine, University of Turku, 20520 Turku, Finland;
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
| | | | - Seija Grenman
- Department of Obstetrics and Gynecology, University of Turku, Turku University Hospital, 20014 Turku, Finland;
| | - Karolina Louvanto
- Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;
- Department of Obstetrics and Gynecology, Tampere University Hospital, 33100 Tampere, Finland
| | - Stina Syrjänen
- Department of Oral Pathology and Radiology, Faculty of Medicine, University of Turku, 20520 Turku, Finland;
- Department of Pathology, University of Turku, Turku University Hospital, 20520 Turku, Finland
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19
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McMullen L, Khoo L, Anderson L, Strasser S, Gracey DM. BK viraemia as a cause of anaemia in after ABO-incompatible liver transplant: a case report. BMC Infect Dis 2023; 23:609. [PMID: 37723433 PMCID: PMC10506278 DOI: 10.1186/s12879-023-08601-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 09/12/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND While anaemia following liver transplant is common, anaemia in the context of BK viraemia is not a commonly recognised phenomenon. CASE PRESENTATION We present the case of 59-year old gentleman with severe anaemia in the context of BK viraemia and nephropathy following ABO incompatible liver transplant. Severity of anaemia appeared to correlate with high titres of BK virus in the serum. Bone marrow biopsy revealed hypocellular marrow with normal cytogenetics. Anaemia improved with treatment with cidofovir, intravenous immunoglobulin, reduction in immunosuppression and erythropoietin stimulating agent. CONCLUSION To our knowledge, this is the first case of anaemia post liver transplant contributed to by BK viraemia.
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Affiliation(s)
- Lucy McMullen
- Renal Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
- University of Sydney School of Medicine, Camperdown, Australia.
| | - Liane Khoo
- Institute of Haematology, Sydney Local Health District, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Lyndal Anderson
- University of Sydney School of Medicine, Camperdown, Australia
- Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia
| | - Simone Strasser
- University of Sydney School of Medicine, Camperdown, Australia
- A W Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - David M Gracey
- Renal Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- University of Sydney School of Medicine, Camperdown, Australia
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20
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Sahragard I, Mohammadi A, Yaghobi R, Pakfetrat M, Afshari A, Sharifi H, Ghaemi M. The relation of NCCR variations and host transcription factors gene regulation in BK polyomavirus infected kidney transplant patients. Gene 2023; 878:147567. [PMID: 37330024 DOI: 10.1016/j.gene.2023.147567] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/24/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND BK polyomavirus (BKPyV) infection in immunocompromised patients can led to polyomavirus-associated nephropathy (BKPyVAN) especially after kidney transplantation. The polyomavirus genome contains enhancer elements that are important transcription activators. In this study, the association between viral and host gene expression and NCCR variations was evaluated in kidney transplant recipients (KTRs) with BKPyV active, and BKPyV in-active infection. METHODS AND RESULTS Blood samples were collected from selected KTRs who divided to patients with active and in-active BKPyV infection. Transcriptional control region (TCR) anatomy was compared to the genomic sequence of archetype BKPyV strain WW using nested PCR method and sequencing. The expression level of some transcription factor genes was evaluated using in-house Real-time PCR (SYBR Green) technique. Most changes were observed after TCR anatomy detection in the Q and P blocks. The expression level of VP1 and LT-Ag viral genes were significantly higher in patients with active infection compared with non-infected ones. Transcription factor genes SP1, NF1, SMAD, NFκB, P53, PEA3, ETS1, AP2, NFAT and AP1 were significantly higher in BKPyV active group in comparison in-active and control groups. The analyses revealed that viral load level and mutations frequency has significant correlation. CONCLUSIONS Based on the results, increasing of NCCR variations were associated with higher viral load of BKPyV especially in Q block. Host transcriptional factors and viral genes all had higher express level in active BKPyV patients versus no in-active ones. Detection of the relation between NCCR variation and BKPyV severity in KTRs need to be confirmed in further complicated studies.
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Affiliation(s)
- Ilnaz Sahragard
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Ali Mohammadi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Ramin Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Maryam Pakfetrat
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afsoon Afshari
- Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Sharifi
- Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Mehran Ghaemi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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21
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Lorentzen EM, Henriksen S, Rinaldo CH. Modelling BK Polyomavirus dissemination and cytopathology using polarized human renal tubule epithelial cells. PLoS Pathog 2023; 19:e1011622. [PMID: 37639485 PMCID: PMC10491296 DOI: 10.1371/journal.ppat.1011622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/08/2023] [Accepted: 08/17/2023] [Indexed: 08/31/2023] Open
Abstract
Most humans have a lifelong imperceptible BK Polyomavirus (BKPyV) infection in epithelial cells lining the reno-urinary tract. In kidney transplant recipients, unrestricted high-level replication of donor-derived BKPyV in the allograft underlies polyomavirus-associated nephropathy, a condition with massive epithelial cell loss and inflammation causing premature allograft failure. There is limited understanding on how BKPyV disseminates throughout the reno-urinary tract and sometimes causes kidney damage. Tubule epithelial cells are tightly connected and have unique apical and basolateral membrane domains with highly specialized functions but all in vitro BKPyV studies have been performed in non-polarized cells. We therefore generated a polarized cell model of primary renal proximal tubule epithelial cells (RPTECs) and characterized BKPyV entry and release. After 8 days on permeable inserts, RPTECs demonstrated apico-basal polarity. BKPyV entry was most efficient via the apical membrane, that in vivo faces the tubular lumen, and depended on sialic acids. Progeny release started between 48 and 58 hours post-infection (hpi), and was exclusively detected in the apical compartment. From 72 hpi, cell lysis and detachment gradually increased but cells were mainly shed by extrusion and the barrier function was therefore maintained. The decoy-like cells were BKPyV infected and could transmit BKPyV to uninfected cells. By 120 hpi, the epithelial barrier was disrupted by severe cytopathic effects, and BKPyV entered the basolateral compartment mimicking the interstitial space. Addition of BKPyV-specific neutralizing antibodies to this compartment inhibited new infections. Taken together, we propose that during in vivo low-level BKPyV replication, BKPyV disseminates inside the tubular system, thereby causing minimal damage and delaying immune detection. However, in kidney transplant recipients lacking a well-functioning immune system, replication in the allograft will progress and eventually cause denudation of the basement membrane, leading to an increased number of decoy cells, high-level BKPyV-DNAuria and DNAemia, the latter a marker of allograft damage.
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Affiliation(s)
- Elias Myrvoll Lorentzen
- Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway
- Metabolic and Renal Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Stian Henriksen
- Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway
- Metabolic and Renal Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Christine Hanssen Rinaldo
- Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway
- Metabolic and Renal Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
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22
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Liu Y, Kong C, Hu H, Zhang Y, Wang T, Qiu T, Zhou J. Risk factors for BK virus infection in DCD donor kidney transplant recipients. Front Med (Lausanne) 2023; 10:1181743. [PMID: 37502357 PMCID: PMC10368890 DOI: 10.3389/fmed.2023.1181743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 06/26/2023] [Indexed: 07/29/2023] Open
Abstract
Background BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention. Methods Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia. Results During a median follow-up time of 1,072 days (range 739-1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5-10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia. Conclusion The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.
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Affiliation(s)
- Yiting Liu
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chenyang Kong
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Haochong Hu
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yalong Zhang
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Tianyu Wang
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Tao Qiu
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jiangqiao Zhou
- Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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23
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Laine HK, Waterboer T, Syrjänen K, Grenman S, Louvanto K, Syrjänen S. Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome. Front Cell Infect Microbiol 2023; 13:1190019. [PMID: 37333846 PMCID: PMC10272380 DOI: 10.3389/fcimb.2023.1190019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 05/17/2023] [Indexed: 06/20/2023] Open
Abstract
Introduction Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Methods Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Results Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Discussion Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.
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Affiliation(s)
- Hanna K. Laine
- Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
- Department of Oral Pathology and Radiology, Faculty of Medicine, University of Turku, Turku, Finland
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Seija Grenman
- Department of Obstetrics and Gynecology, University of Turku, Turku University Hospital, Turku, Finland
| | - Karolina Louvanto
- Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland
| | - Stina Syrjänen
- Department of Oral Pathology and Radiology, Faculty of Medicine, University of Turku, Turku, Finland
- Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland
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24
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Sorin MN, Di Maio A, Silva LM, Ebert D, Delannoy CP, Nguyen NK, Guerardel Y, Chai W, Halary F, Renaudin-Autain K, Liu Y, Bressollette-Bodin C, Stehle T, McIlroy D. Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus. Cell Rep 2023; 42:112114. [PMID: 36790933 PMCID: PMC9989821 DOI: 10.1016/j.celrep.2023.112114] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 12/19/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.
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Affiliation(s)
- Marie N Sorin
- Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
| | - Antonio Di Maio
- Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Lisete M Silva
- Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Domenic Ebert
- Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
| | - Clément P Delannoy
- Université de Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
| | - Ngoc-Khanh Nguyen
- Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France
| | - Yann Guerardel
- Université de Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan
| | - Wengang Chai
- Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Franck Halary
- Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France
| | | | - Yan Liu
- Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Céline Bressollette-Bodin
- Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; CHU Nantes Laboratoire de Virologie, Nantes, France; Faculté de Médecine, Nantes Université, Nantes, France
| | - Thilo Stehle
- Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
| | - Dorian McIlroy
- Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; Faculté des Sciences et des Techniques, Nantes Université, Nantes, France.
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25
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Characteristics, risk factors and outcome of BKV nephropathy in kidney transplant recipients: a case-control study. BMC Infect Dis 2023; 23:74. [PMID: 36747162 PMCID: PMC9903532 DOI: 10.1186/s12879-023-08043-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/30/2023] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Following kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR. METHODS We conducted a retrospective case-control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan-Meier estimator. RESULTS Sixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5-14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm3 and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01). CONCLUSIONS BKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm3 and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis.
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26
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Hamed R, Al Maghrabi M, Kasem MF, El Fekky MA, Al Shami AA, Mohamed NH, Sheyyab A. Screening for polyomavirus nephropathy and viremia in children with renal transplantation. Pediatr Transplant 2023; 27:e14479. [PMID: 36724736 DOI: 10.1111/petr.14479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 10/29/2022] [Accepted: 01/13/2023] [Indexed: 02/03/2023]
Abstract
BACKGROUND Polyomavirus, known as BK virus, is an important cause of allograft dysfunction in renal transplant patients, leading to BK virus nephropathy. The main study objectives were to assess the disease incidence and disease course in pediatric patients, and assess the diagnostic accuracy of BK screening for asymptomatic patients. METHODS This is a single-center observational study, which included 81 pediatric renal allograft recipients that were transplanted and/or followed at King Fahad Specialist Hospital-Dammam, Saudi Arabia. Screening for BK virus was performed prospectively according to a predetermined hospital protocol. Our BK screening protocol consisted of periodic quantitative real time polymerase chain reaction test in the plasma. In patients with deranged graft function, graft biopsies were evaluated for the presence of BK nephropathy. RESULTS Our study detected BK viremia in 14 patients (17.3%), while BK nephropathy occurred in seven patients (8.6%). The onset of BK viremia had bimodal distribution, 78 percent occurring within first year post-transplantation, while 21.4% occurred late. Patients who developed BK nephropathy had a higher BK level than BK viremia patients, for both mean and peak values (p = .02, p = .02). A BK cutoff level of 40 000 copies/mL showed sensitivity and specificity of 85.7%, 85.7%, respectively, in predicting the conversion of BK viremia to BK nephropathy. CONCLUSIONS BK viremia and BK nephropathy occur in pediatric patients with similar incidence rates compared to adult patients. Protocolized screening led to early detection of viremia, and could predict the conversion of BK viremia to BK nephropathy and allow for early immunosuppression modulation.
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Affiliation(s)
- Radi Hamed
- Department of Pediatrics, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | - Mohammed Al Maghrabi
- The Division of Pediatric Nephrology, Department of Pediatrics, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Mohammed F Kasem
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed AbdelRaheem El Fekky
- The Division of Pediatric Nephrology, Department of Pediatrics, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | - Al-Anoud Al Shami
- The Department of Pathology, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia
| | | | - Ahmad Sheyyab
- Department of Medicine, Faculty of Medicine, The Hashemite University, Zarqa, Jordan
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27
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Seroprevalence of polyomaviruses BK and JC in Finnish women and their spouses followed-up for three years. Sci Rep 2023; 13:879. [PMID: 36650213 PMCID: PMC9845201 DOI: 10.1038/s41598-023-27850-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 01/09/2023] [Indexed: 01/18/2023] Open
Abstract
BK (BKPyV) and JC (JCPyV) polyomavirus infections are commonly subclinical and known infrequently to cause serious clinical diseases. Longitudinal follow-up studies regarding JCPyV and BKPyV serological outcomes are scanty. We analyzed JCPyV and BKPyV IgG-antibodies in 327 pregnant women and their 132 spouses, enrolled in the longitudinal Finnish Family HPV cohort at Turku University Hospital, Finland. Blood samples taken at baseline, and at 12-, 24-, and 36-month follow-up visits were analyzed for capsid protein VP1-antibodies using multiplex serology. Seroprevalence was constant for both BKPyV and JCPyV across the follow-up, varying between 95-99% and 59-68%, respectively, in women and between 96-97% and 66-72%, respectively, in their spouses. Seroconversion to BKPyV and JCPyV was detected in 15% and 18% of the women and in 13% and 19% of the men, respectively. Waning of BKPyV and JCPyV antibodies was infrequent, present in only 5% of the women (both viruses) and in 1.5% of the male spouses (only BKPyV). The number of lifetime sexual partners (p = 0.038) was lower among JCPyV seropositive men. To conclude, seropositivity to BKPyV and JCPyV is common among marital couples in Finland, with only slight differences between genders. In men, the sexual behavior might be associated with JCPyV seroprevalence.
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28
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Miglietta F, Iamartino L, Palmini G, Giusti F, Marini F, Iantomasi T, Brandi ML. Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism. Front Endocrinol (Lausanne) 2023; 13:1085315. [PMID: 36714597 PMCID: PMC9877332 DOI: 10.3389/fendo.2022.1085315] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/26/2022] [Indexed: 01/13/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger post-operative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well.
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Affiliation(s)
- Francesca Miglietta
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Luca Iamartino
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Gaia Palmini
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Francesca Giusti
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Francesca Marini
- Fondazione FIRMO Onlus (Italian Foundation for the Research on Bone Diseases), Florence, Italy
| | - Teresa Iantomasi
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Maria Luisa Brandi
- Fondazione FIRMO Onlus (Italian Foundation for the Research on Bone Diseases), Florence, Italy
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29
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Conversion to mTOR-Inhibitors Plus IV Immunoglobulins in Kidney-Transplant Recipients with BKV Infection: A Retrospective Comparative Study. J Clin Med 2022; 11:jcm11247292. [PMID: 36555909 PMCID: PMC9785214 DOI: 10.3390/jcm11247292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/02/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
BK virus-associated nephropathy (PvAN) increases the risk of graft failure justifying treatment. Conversion to mammalian target of rapamycin inhibitors (mTORi) and Human polyclonal immunoglobulins (IVIg) could prevent the risk of PvAN. Our retrospective study assessed the efficacy of mTORi associated with IVIg therapy (mTORi±IVIg group) versus standard immunosuppression reduction to clear BKV DNAemia. Among forty-three kidney-transplanted patients with positive BKV DNAemia, we included twenty-six patients in the mTORi±IVIg group and reduced immunosuppression therapy for seventeen patients. We focused on BKV DNAemia clearance on the first-year. Renal function, rejection rate, evolution to PvAN, and complications of immunosuppression were assessed. BKV DNAemia decreased faster and significantly in the control group as compared to the mTORi±IVIg group (p < 0.001). Viral clearance was significantly higher in the control group compared to the mTORi±IVIg group (88% vs. 58%; p = 0.033). Death-censored graft loss, rejection rates and kidney-graft function at 12 months did not significantly differ. Multivariate analyses significantly associated BKV DNAemia clearance with reducing immunosuppression (OR = 0.11 (0.06−0.9), p = 0.045), female kidney donor (OR = 0.10 (0.01−0.59/)], p = 0.018) and time to first DNAemia, (OR = 0.88 (0.76−0.96), p = 0.019). In our study, the standard treatment for BKV DNAemia had better outcomes than an mTORi±IVIg conversion.
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Yaghobi R, Afshari A, Roozbeh J. Host and viral
RNA
dysregulation during
BK
polyomavirus
infection in kidney transplant recipients. WIRES RNA 2022:e1769. [DOI: 10.1002/wrna.1769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 11/12/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Affiliation(s)
- Ramin Yaghobi
- Shiraz Transplant Research Center Shiraz University of Medical Sciences Shiraz Iran
| | - Afsoon Afshari
- Shiraz Nephro‐Urology Research Center Shiraz University of Medical Sciences Shiraz Iran
| | - Jamshid Roozbeh
- Shiraz Nephro‐Urology Research Center Shiraz University of Medical Sciences Shiraz Iran
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Lack of predictive capacity of pre-transplant anti-BK virus antibodies for post-transplant reactivation. J Nephrol 2022; 36:1071-1073. [DOI: 10.1007/s40620-022-01487-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 10/01/2022] [Indexed: 12/03/2022]
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Uzay A, Gündoğdu Y, Koşan B, Yetiş T, Gür H, Okuturlar Y, Kartı SS. Daily low dose intravesical cidofovir for the treatment of BK virus associated hemorrhagic cystitis after allogeneic stem cell transplantation. J Infect Chemother 2022; 29:67-71. [PMID: 36162643 DOI: 10.1016/j.jiac.2022.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/01/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022]
Abstract
INTRODUCTION BK virus associated hemorrhagic cystitis(BKV-AHC) is a serious complication observed after allogeneic stem cell transplantation and the current therapeutic options are scarce with substantial renal side effects. Although the guidelines recommend intravenous cidofovir application with caution to nephrotoxicity, there are few studies which investigated intravesical administration and reported similar therapeutic results with less renal side effects. METHODS We administered low dose, daily and consecutive (75 mg/day, for 5 days) intravesical cidofovir to 25 patients with BKV-AHC that developed after (ASCT). RESULTS The response rate in our cohort was 92% and relapse was not encountered in 84% of the patient population during one year of follow-up. The median BK urine viral load significantly decreased from 260,000,000 IU/mL to 53,000,000 IU/mL after a week of treatment (p = 0.0001). Rise in serum creatinine was observed in 5 patients during treatment and post-treatment nephrotoxicity was seen in only 1 patient. CONCLUSIONS Daily low dose intravesical cidofovir might be an effective treatment option for BKV-AHC after ASCT with favorable less systemic side effects.
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Affiliation(s)
- Ant Uzay
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Hematology and Stem Cell Transplantation, Turkey
| | - Yasemin Gündoğdu
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Internal Medicine, Turkey.
| | - Barış Koşan
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Internal Medicine, Turkey
| | - Tuğba Yetiş
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Clinical Nursing, Turkey
| | - Hatun Gür
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Internal Medicine, Turkey
| | - Yildiz Okuturlar
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Internal Medicine, Turkey
| | - S Sami Kartı
- Acıbadem Mehmet Ali Aydınlar University, School of Medicine, Department of Hematology and Stem Cell Transplantation, Turkey
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韩 冠, 许 洋, 李 志, 孟 畅, 朱 宏, 杨 昆, 周 利, 李 学. [Ureteral stenosis following hematopoietic stem cell transplantation: A case report]. BEIJING DA XUE XUE BAO. YI XUE BAN = JOURNAL OF PEKING UNIVERSITY. HEALTH SCIENCES 2022; 54:762-765. [PMID: 35950405 PMCID: PMC9385521 DOI: 10.19723/j.issn.1671-167x.2022.04.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Indexed: 06/15/2023]
Abstract
Ureteral stenosis is a comparatively rare complication following hematopoietic stem cell transplantation (HSCT). The etiology is still unclear and most believe that this may be due to the reactivation of BK virus in a state of immunodeficiency. In the later stages of ureteral stenosis with scarring, invasive interventions must be taken to relieve the hydronephrosis. Common treatments, such as D-J stent placement and permanent nephrostomy may not only entail the risk of infection, but also seriously affect the quality of life. Few cases of surgical intervention have been reported. In this article, a 25-year-old female was admitted to Peking University First Hospital suffering from recurrent flank pain. Seven years before, she developed hemorrhagic cystitis and bilateral urethritis 40 days after allogeneic HSCT. After continuous bladder irrigation and antiviral therapy, the left-sided hydronephrosis gradually alleviated while the right-sided one did not improve. D-J stents were used for urine drainage for 7 years before percuta-neous nephrostomy. Preoperative antegrade pyelography revealed significant hydronephrosis in the right kidney with long stricture of proximal-middle ureter. After comprehensive decision, she underwent ileal ureter replacement. The operation was successful. The segmental lesion was dissected and the scar tissue was removed. A 25 cm intestinal tube was isolated to connect the pelvis and bladder. An anti-reflux nipple was created at the distal end of ileal ureter to prevent the potential infection. The blood loss was minimal. After surgery, the drainage tube was removed in 2 weeks, the nephrostomy tube and the D-J stent was removed in 3 months. Follow-up mainly included clinical assessment, serologic testing, renal ultrasonography, blood gas analysis and radiological examination. During the follow-up of 6 years, she was symptom-free and no postoperative complications occurred. The serum creatinine level was stable. No hydronephrosis was observed under ultrasonography. Obvious peristaltic waves and ureteral jets of the ileal ureter was confirmed on cine magnetic resonance urography. To sum up, ureteral stenosis after HSCT is relatively rare. Obstruction caused by scarring is usually irreversible and surgical intervention should be designed according to the location and length of the lesion. Ileal ureter replacement can be a safe, feasible and effective method to solve this kind of complex stricture.
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Affiliation(s)
- 冠鹏 韩
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 洋洋 许
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 志华 李
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 畅 孟
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 宏建 朱
- 北京市健宫医院泌尿外科，北京 100054Department of Urology, Beijing Jiangong Hospital, Beijing 100054, China
| | - 昆霖 杨
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 利群 周
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
| | - 学松 李
- 北京大学第一医院泌尿外科，北京大学泌尿外科研究所，国家泌尿、男性生殖系肿瘤研究中心，北京 100034Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Cancer Center, Beijing 100034, China
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A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome. Int Urogynecol J 2022; 33:2557-2563. [PMID: 35881178 DOI: 10.1007/s00192-022-05298-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/27/2022] [Indexed: 02/05/2023]
Abstract
INTRODUCTION AND HYPOTHESIS To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.
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BK Virus Infection and BK-Virus-Associated Nephropathy in Renal Transplant Recipients. Genes (Basel) 2022; 13:genes13071290. [PMID: 35886073 PMCID: PMC9323957 DOI: 10.3390/genes13071290] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/18/2022] [Accepted: 07/20/2022] [Indexed: 01/27/2023] Open
Abstract
Poliomavirus BK virus (BKV) is highly infective, causing asymptomatic infections during childhood. After the initial infection, a stable state of latent infection is recognized in kidney tubular cells and the uroepithelium with negligible clinical consequences. BKV is an important risk factor for BKV-associated diseases, and, in particular, for BKV-associated nephropathy (BKVN) in renal transplanted recipients (RTRs). BKVN affects up to 10% of renal transplanted recipients, and results in graft loss in up to 50% of those affected. Unfortunately, treatments for BK virus infection are restricted, and there is no efficient prophylaxis. In addition, consequent immunosuppressive therapy reduction contributes to immune rejection. Increasing surveillance and early diagnosis based upon easy and rapid analyses are resulting in more beneficial outcomes. In this report, the current status and perspectives in the diagnosis and treatment of BKV in RTRs are reviewed.
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Demey B, Bentz M, Descamps V, Morel V, Francois C, Castelain S, Helle F, Brochot E. BK Polyomavirus bkv-miR-B1-5p: A Stable Micro-RNA to Monitor Active Viral Replication after Kidney Transplantation. Int J Mol Sci 2022; 23:ijms23137240. [PMID: 35806242 PMCID: PMC9266457 DOI: 10.3390/ijms23137240] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 06/26/2022] [Accepted: 06/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Bkv-miR-B1-5p is a viral micro-RNA (miRNA) specifically produced during BK polyomavirus (BKPyV) replication. Recent studies have suggested using bkv-miR-B1-5p as a biomarker to monitor viral infection and predict complications in kidney transplant patients. To identify the technical limitations of this miRNA quantification in biological samples, knowledge of its stability and distribution in the extracellular compartment is necessary. Moreover, a proof of concept for using bkv-miR-B1-5p as a biomarker of active replication in chronic infection is still missing in the published literature. Methods: The stability of bkv-miR-B1-5p was evaluated in samples derived from cell cultures and in urine from BKPyV-infected kidney transplant recipients. The miRNA was quantified in different fractions of the extracellular compartment, including exosomes, and protein binding was evaluated. Finally, we developed an in vitro model for chronic culture of BKPyV clinical isolates to observe changes in the bkv-miR-B1-5p level during persistent infections. Results: Bkv-miR-B1-5p is a stable biomarker in samples from humans and in vitro experiments. Marginally associated with the exosomes, most of the circulating bkv-miR-B1-5p is bound to proteins, especially Ago2, so the miRNA quantification does not require specific exosome isolation. The bkv-miR-B1-5p level is predictable of viral infectivity, which makes it a potential specific biomarker of active BKPyV replication after kidney transplantation.
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Affiliation(s)
- Baptiste Demey
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
- Correspondence: (B.D.); (E.B.); Tel.: +33-322087065 (B.D.)
| | - Marine Bentz
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Véronique Descamps
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Virginie Morel
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Catherine Francois
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Sandrine Castelain
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Francois Helle
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
| | - Etienne Brochot
- Laboratoire de Virologie, Centre Hospitalier Universitaire, F-80000 Amiens, France; (V.D.); (V.M.); (C.F.); (S.C.)
- UR UPJV 4294, Agents Infectieux, Résistance et Chimiothérapie (AGIR), Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, F-80000 Amiens, France; (M.B.); (F.H.)
- Correspondence: (B.D.); (E.B.); Tel.: +33-322087065 (B.D.)
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The effect of BK polyomavirus large T antigen on CD4 and CD8 T cells in kidney transplant recipients. Transpl Immunol 2022; 74:101655. [PMID: 35777612 DOI: 10.1016/j.trim.2022.101655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/01/2022] [Accepted: 06/22/2022] [Indexed: 11/20/2022]
Abstract
Human BK polyomavirus (BKPyV) can affect the machinery of the host cell to induce optimal viral replication or transform them into tumor cells. Reactivation of BKPyV happens due to immunosuppression therapies following renal transplantation which might result in BK polyomavirus nephropathy (BKPyVAN) and allograft loss. The first protein that expresses after entering into host cells and has an important role in pathogenicity is the Large T antigen (LT-Ag). In this review tries to study the molecular and cellular inter-regulatory counteractions especially between CD4 and CD8 T cells, and BKPyV LT-Ag may have role in nephropathy after renal transplantation.
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Yang D, Zhuang B, Wang Y, Huang G, Xu M, Lin M, Wang W, Huang G, Wang C, Xie X, Xie X. High-Frequency US for BK Polyomavirus-associated Nephropathy after Kidney Transplant. Radiology 2022; 304:333-341. [PMID: 35503018 DOI: 10.1148/radiol.211855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Background BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of chronic renal allograft dysfunction. However, US features indicative of BKPyVAN have not been fully evaluated. Purpose To assess the value of high-frequency US for the diagnosis of BKPyVAN in kidney transplant recipients. Materials and Methods In this prospective cohort study, participants who tested positive for BK viruria after kidney transplant from September 2019 to January 2021 were evaluated with high-frequency US 1 day before biopsy. Clinical characteristics and US features were compared between participants with and without BKPyVAN. Significant predictors associated with BKPyVAN were determined using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results A total of 105 participants who underwent kidney transplant (mean age, 38 years ± 11 [SD]; 63 men) were evaluated; 45 participants were diagnosed with BKPyVAN. Multivariable analysis demonstrated that eccentric hydronephrosis and subcapsular hypoechoic areas were independent factors for BKPyVAN. The AUC for predicting BKPyVAN according to subcapsular hypoechoic areas was 0.66 (95% CI: 0.55, 0.77), with a specificity of 92% (55 of 60 participants). The AUC of combined US (eccentric hydronephrosis plus subcapsular hypoechoic area) and clinical (urine BKPyV DNA load [BKPyV-DNA] plus BK viremia) features was 0.90, with a specificity of 92% (55 of 60 participants). Parenchymal hyperechoic and subcapsular hypoechoic areas were independent factors for differentiating BKPyVAN from transplant rejection. The pooled specificity of subcapsular hypoechoic areas was 96% (21 of 22 participants), with an AUC of 0.67 (95% CI: 0.54, 0.80). For the combination of US (parenchymal echogenicity plus subcapsular hypoechoic area) and clinical (urine BKPyV-DNA plus time since transplant) features, the AUC reached 0.92 and specificity was 82% (18 of 22 participants). Conclusion High-frequency US characteristics are valuable for diagnosing BK polyomavirus-associated nephropathy (BKPyVAN) and distinguishing BKPyVAN from rejection in kidney transplant recipients. Online supplemental material is available for this article. © RSNA, 2022.
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Affiliation(s)
- Daopeng Yang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Bowen Zhuang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Yan Wang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Gang Huang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Ming Xu
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Manxia Lin
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Wei Wang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Guangliang Huang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Changxi Wang
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Xiaoyan Xie
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
| | - Xiaohua Xie
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (D.Y., B.Z., Y.W., M.X., M.L., W.W., Guangliang Huang, Xiaoyan Xie, Xiaohua Xie) and Organ Transplant Center (Gang Huang, C.W.), The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Rd 2, Guangzhou 510080, People's Republic of China
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Komorniczak M, Król E, Lizakowski S, Dębska-Ślizień A. Screening for Polyomavirus Viruria Like Early Detection of Human Polyomavirus Infection and Replication: The Results of a Single-Center Observation. Transplant Proc 2022; 54:989-994. [DOI: 10.1016/j.transproceed.2022.02.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 02/18/2022] [Indexed: 11/17/2022]
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40
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Chan S, Howell M, Johnson DW, Hawley CM, Tong A, Craig JC, Cao C, Blumberg E, Brennan D, Campbell SB, Francis RS, Huuskes BM, Isbel NM, Knoll G, Kotton C, Mamode N, Muller E, Biostat EMPM, An HPH, Tedesco-Silva H, White DM, Viecelli AK. Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers and health professionals. Clin Transplant 2022; 36:e14660. [PMID: 35362617 DOI: 10.1111/ctr.14660] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/07/2022] [Accepted: 03/29/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS In an international online survey, participants rated the absolute importance of 16 infections and 8 severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, 8 who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5 respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1) and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top 3 most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top 3 severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Samuel Chan
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Translational Research Institute, Brisbane, Queensland, Australia
| | - Martin Howell
- Sydney School of Public Health, Faculty of Medicine and Health.,Centre for Kidney Research, The Children's Hospital at Westmead, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Translational Research Institute, Brisbane, Queensland, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Translational Research Institute, Brisbane, Queensland, Australia
| | - Allison Tong
- Sydney School of Public Health, Faculty of Medicine and Health.,Centre for Kidney Research, The Children's Hospital at Westmead, Australia
| | - Jonathan C Craig
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Christopher Cao
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Emily Blumberg
- Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Daniel Brennan
- Division of Nephrology, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Scott B Campbell
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Ross S Francis
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Brooke M Huuskes
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Victoria, Australia
| | - Nicole M Isbel
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Greg Knoll
- Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa
| | - Camille Kotton
- Transplant and Immunocompromised Host Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Nizam Mamode
- Department of Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, SE1 9RT, United Kingdom
| | - Elmi Muller
- Department of Surgery, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - Elaine M Pascoe M Biostat
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Ha Phan Hai An
- Department of Internal Medicine, Division of Nephrology, Viet Duc Hospital, Hanoi Medical University, Vietnam
| | - Helio Tedesco-Silva
- Division of Nephrology, Hospital do Rim, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | | | - Andrea K Viecelli
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Translational Research Institute, Brisbane, Queensland, Australia
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41
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Zhao J, You X, Zeng X. Research progress of BK virus and systemic lupus erythematosus. Lupus 2022; 31:522-531. [PMID: 35264023 DOI: 10.1177/09612033221084259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients are often infected by viruses due to deficient immunity or immunosuppressant use. BK virus (BKV)mainly affects the kidney and can also cause multiple organ involvement throughout the body, which is similar to SLE. BKV is mostly a latent infection in vivo. The incidence of virus reactivation is higher in SLE patients. Reactivation of BKV can induce the production of autoantibodies, thereby promoting the occurrence and development of SLE.Purpose: Aim of this article is to review the prevalence and pathegenesis of BKV infection in SLE patients.Method: The literature search was conducted using four different databases including PubMed, Cochrane Library, Scopus and Web of Science.Results: BK virus is higher infection and reactivation in SLE patients. The "hapten carrier" mechanism may lead to the production of autoantibodies. Some immunosuppressive drugs, like leflumide and hydroxychloroquine, may show a protective effect.Conclusions: BKV infection plays a role in the occurrence and development of SLE, and its significance deserves further exploration.
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Affiliation(s)
- Jiawei Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
| | - Xin You
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 34732Peking Union Medical College, Beijing, China
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42
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Miyata M, Ichikawa K, Matsuki E, Watanabe M, Peltier D, Toubai T. Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation. Front Immunol 2022; 12:779881. [PMID: 35058924 PMCID: PMC8763685 DOI: 10.3389/fimmu.2021.779881] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 12/02/2021] [Indexed: 12/30/2022] Open
Abstract
Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targets the intestines, liver, and skin. However, recent studies suggest aGVHD may also attack the kidney and contribute to AKI following allo-HCT. For example, severe aGVHD is associated with AKI, suggesting a link between the two. In addition, animal models have shown donor immune cell infiltration and increased expression of inflammatory cytokines in recipient kidneys after allo-HCT. Therefore, aGVHD may also target the kidney and contribute to AKI following allo-HCT. Herein, we describe the etiology, diagnosis, risk factors, pathophysiology, prevention, and treatment of renal injury after allo-HCT. In addition, we highlight emerging evidence that aGVHD may contribute to the development of AKI after allo-HCT.
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Affiliation(s)
- Masahiro Miyata
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Kazunobu Ichikawa
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Eri Matsuki
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Masafumi Watanabe
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Daniel Peltier
- Department of Pediatric Hematology/Oncology, University Michigan Medical School, Ann Arbor, MI, United States
| | - Tomomi Toubai
- Department of Internal Medicine III, Division of Hematology and Cell Therapy, Faculty of Medicine, Yamagata University, Yamagata, Japan
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43
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Wang J, Li J, Chen Z, Xu M, Yang C, Rong R, Zhu T. A Nomogram for Predicting BK Virus Activation in Kidney Transplantation Recipients Using Clinical Risk Factors. Front Med (Lausanne) 2022; 9:770699. [PMID: 35223891 PMCID: PMC8866320 DOI: 10.3389/fmed.2022.770699] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
BK virus is a common opportunistic viral infection that could cause BK virus-associated nephropathy in renal transplant recipients. Thus, we retrospectively analyzed clinical and laboratory data associated with a higher risk of BK virus activation from 195 renal transplant recipients by the multivariate logistic regression analysis and performed the external validation. Results showed that patients with BK virus active infection were associated with a deceased donor, had lower direct bilirubin levels, a higher proportion of albumin in serum protein electrophoresis, and lower red blood cells and neutrophil counts. The multivariate logistic regression analyses revealed that the living donor, direct bilirubin, and neutrophil counts were significantly associated with BK virus activation. The logistic regression model displayed a modest discriminability with the area under the receiver operating characteristic curve of 0.689 (95% CI: 0.607–0.771; P < 0.01) and also demonstrated a good performance in the external validation dataset (the area under the receiver operating characteristic curve was 0.699, 95% CI: 0.5899–0.8081). The novel predictive nomogram achieved a good prediction of BK virus activation in kidney transplant recipients.
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Affiliation(s)
- Jiyan Wang
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Jiawei Li
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Zhongli Chen
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Xu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Cheng Yang
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
- Zhangjiang Institute of Fudan University, Shanghai, China
- *Correspondence: Cheng Yang ;
| | - Ruiming Rong
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
- Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, China
- Ruiming Rong
| | - Tongyu Zhu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
- Tongyu Zhu ;
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44
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Jarasvaraparn C, Choudhury S, Rusch C, Nadler M, Liss KH, Stoll J, Hmiel S, Khan A, Doyle M, Kulkarni S. Characteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in children. Pediatr Transplant 2022; 26:e14131. [PMID: 34494348 PMCID: PMC10591294 DOI: 10.1111/petr.14131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 08/17/2021] [Accepted: 08/20/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND While prior adult studies have shown that approximately 20%-38% of subjects undergoing solid-organ transplant develop neutropenia, similar analyses in pediatric subjects are scarce. METHODS We conducted a retrospective chart review of liver transplant (LT) and kidney transplant (KT) recipients at our center during the period 2008-2018. All of the KT and none of the LT subjects during this time period had induction with either anti-thymocyte globulin (ATG) or basiliximab at time of transplant. Neutropenia was defined as absolute neutrophil count (ANC) value ≤1000/mm3 . RESULTS One hundred subjects with LT and 82 subjects with KT were included. The incidence of neutropenia within the first year of transplant in KT was higher compared to LT (54.8% vs 39%, p = .01). The median number of hospitalizations (p = .001) and infectious complications (p = .04) was significantly higher only in the KT subjects who developed neutropenia (compared to those who did not). Multivariate analysis identified factors associated with severity of liver disease at transplant, namely h/o upper gastrointestinal bleeding (p = .02), weight deficit (p = .01), and pre-LT ANC (p = .01), along with high or moderate risk cytomegalovirus status (p = .05) as predictors of neutropenia in LT subjects. Female gender (p = .03) predicted neutropenia, while BK virus infection was protective for neutropenia (p = .04) in KT subjects. CONCLUSIONS The incidence of and morbidity associated with neutropenia within 1 year post-transplant is higher in KT subjects compared to LT subjects. The likely reason for this is the use of induction therapy (ATG, basiliximab) at the time of transplant in KT subjects.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Shelley Choudhury
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Courtney Rusch
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Michelle Nadler
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Kim H.H. Liss
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Janis Stoll
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Stanley Hmiel
- Department of Pediatrics, Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Adeel Khan
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Maria Doyle
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sakil Kulkarni
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
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45
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Li N, Huang XJ, Wang Y, Suo P, Xu LP, Liu KY, Zhang XH, Yan CH, Wang FR, Kong J, Cheng YF. [BK virus encephalitis in children with hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2021; 42:823-827. [PMID: 34788921 PMCID: PMC8607018 DOI: 10.3760/cma.j.issn.0253-2727.2021.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
目的 探讨异基因造血干细胞移植患儿中BK病毒（BKV）脑炎的发病率、病死率、中位发病时间、临床表现、诊治及转归等，以提高临床医师对本病的认识。 方法 回顾性分析2015年1月1日至2020年12月31日在北京大学人民医院接受单倍型造血干细胞移植治疗的709例儿童患者，其中14例诊断为BKV脑炎，分析其临床特征、治疗过程及转归。 结果 BKV脑炎发生率为1.97％（14例）。患儿多为男性（12例），中位年龄为11岁，中位发病时间为移植后第55天。最常见的临床表现为意识障碍、抽搐发作（7例）。14例患儿予阿昔洛韦、更昔洛韦单用，或联合丙种球蛋白治疗，9例患儿痊愈，1例患儿死于病毒性脑炎，4例患儿死于其他疾病，病死率为35.7％。 结论 BKV脑炎主要表现为脑炎或脑膜炎。虽然确诊BKV脑炎后积极予药物治疗，但许多患者仍死于多器官衰竭或其他并发症。当异基因造血干细胞移植患者出现神经系统症状、出血性膀胱炎时，必须高度警惕BKV脑炎，尽早施救，从而改善患者的生存率及生活质量。
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Affiliation(s)
- N Li
- Peking University People's Hospital,Beijing 100044,China Xingtai People's Hospital, Xingtai 054000, China
| | - X J Huang
- Peking University People's Hospital,Beijing 100044,China
| | - Y Wang
- Peking University People's Hospital,Beijing 100044,China
| | - P Suo
- Peking University People's Hospital,Beijing 100044,China
| | - L P Xu
- Peking University People's Hospital,Beijing 100044,China
| | - K Y Liu
- Peking University People's Hospital,Beijing 100044,China
| | - X H Zhang
- Peking University People's Hospital,Beijing 100044,China
| | - C H Yan
- Peking University People's Hospital,Beijing 100044,China
| | - F R Wang
- Peking University People's Hospital,Beijing 100044,China
| | - J Kong
- Peking University People's Hospital,Beijing 100044,China
| | - Y F Cheng
- Peking University People's Hospital,Beijing 100044,China
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Vishnevetsky A, Anand P. Approach to Neurologic Complications in the Immunocompromised Patient. Semin Neurol 2021; 41:554-571. [PMID: 34619781 DOI: 10.1055/s-0041-1733795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Neurologic complications are common in immunocompromised patients, including those with advanced human immunodeficiency virus, transplant recipients, and patients on immunomodulatory medications. In addition to the standard differential diagnosis, specific pathogens and other conditions unique to the immunocompromised state should be considered in the evaluation of neurologic complaints in this patient population. A thorough understanding of these considerations is critical to the inpatient neurologist in contemporary practice, as increasing numbers of patients are exposed to immunomodulatory therapies. In this review, we provide a chief complaint-based approach to the clinical presentations and diagnosis of both infectious and noninfectious complications particular to immunocompromised patients.
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Affiliation(s)
- Anastasia Vishnevetsky
- Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Pria Anand
- Department of Neurology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
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47
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Virus-Induced Tumorigenesis and IFN System. BIOLOGY 2021; 10:biology10100994. [PMID: 34681093 PMCID: PMC8533565 DOI: 10.3390/biology10100994] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/01/2021] [Accepted: 09/27/2021] [Indexed: 01/11/2023]
Abstract
Oncogenic viruses favor the development of tumors in mammals by persistent infection and specific cellular pathways modifications by deregulating cell proliferation and inhibiting apoptosis. They counteract the cellular antiviral defense through viral proteins as well as specific cellular effectors involved in virus-induced tumorigenesis. Type I interferons (IFNs) are a family of cytokines critical not only for viral interference but also for their broad range of properties that go beyond the antiviral action. In fact, they can inhibit cell proliferation and modulate differentiation, apoptosis, and migration. However, their principal role is to regulate the development and activity of most effector cells of the innate and adaptive immune responses. Various are the mechanisms by which IFNs exert their effects on immune cells. They can act directly, through IFN receptor triggering, or indirectly by the induction of chemokines, the secretion of further cytokines, or by the stimulation of cells useful for the activation of particular immune cells. All the properties of IFNs are crucial in the host defense against viruses and bacteria, as well as in the immune surveillance against tumors. IFNs may be affected by and, in turn, affect signaling pathways to mediate anti-proliferative and antiviral responses in virus-induced tumorigenic context. New data on cellular and viral microRNAs (miRNAs) machinery, as well as cellular communication and microenvironment modification via classical secretion mechanisms and extracellular vesicles-mediated delivery are reported. Recent research is reviewed on the tumorigenesis induced by specific viruses with RNA or DNA genome, belonging to different families (i.e., HPV, HTLV-1, MCPyV, JCPyV, Herpesviruses, HBV, HCV) and the IFN system involvement.
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48
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Torres R, Montero C, Escobar C, Reina M, Acevedo A, Yomayusa N, Gayón D, Pérez J. Early Detection Strategy of BK Polyomavirus Nephropathy in Patients undergoing Renal Transplant: A Single-Center Retrospective Study. TRANSPLANTATION REPORTS 2021. [DOI: 10.1016/j.tpr.2021.100077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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49
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Patel H, Rodig N, Agrawal N, Cardarelli F. Incidence and risk factors of kidney allograft loss due to BK nephropathy in the pediatric population: A retrospective analysis of the UNOS/OPTN database. Pediatr Transplant 2021; 25:e13927. [PMID: 33245596 DOI: 10.1111/petr.13927] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/16/2020] [Accepted: 10/29/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND BK virus infection can lead to graft dysfunction and loss in kidney transplant recipients. Risk factors for BKV and BKVN have been inadequately studied in children. Here, we evaluate the incidence and risk factors of allograft loss due to BKVN in the pediatric population of the UNOS data set. METHODS We conducted a retrospective cohort analysis of the UNOS database and identified all pediatric recipients of kidney transplantation between 2000 and 2018. We compared donor and recipient characteristics, including cause of ESRD, among patients who lost their graft due to BKVN or other causes, and those with functioning allograft. Kaplan-Meier curve and Cox regression analysis were performed to evaluate the risk factors. RESULTS A total of 66 patients (0.47%) suffered graft failure from BKVN. Older age, male gender, HLA mismatch, and rejection at 1 year were significantly associated with BKVN graft failure, compared to recipients with functioning allograft. In comparison with graft loss due to other causes, male gender, higher HLA mismatch, rejection in 1st year and tacrolimus use at discharge were significantly associated with BKVN graft loss. Recipients who received mycophenolate at time of discharge were at reduced risk for BKVN graft failure. Compared to graft failure from other causes, BKVN graft failure had shorter death censored graft survival [P = .001]. ESRD due to urologic causes and Alport syndrome had higher rate of BKVN graft failure. CONCLUSION Incidence of graft loss from BKVN in the pediatric population was 10.2 per 10 000 patient-years in this study. BKVN is associated with early allograft failure in the pediatric population, compared to other causes of graft loss. Male gender, HLA mismatch, rejection in 1st year, and urological cause of ESRD are risk factors for graft failure from BKVN in children.
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Affiliation(s)
- Het Patel
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Nancy Rodig
- Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - Nikhil Agrawal
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Francesca Cardarelli
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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50
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Furmaga J, Kowalczyk M, Zapolski T, Furmaga O, Krakowski L, Rudzki G, Jaroszyński A, Jakubczak A. BK Polyomavirus-Biology, Genomic Variation and Diagnosis. Viruses 2021; 13:1502. [PMID: 34452367 PMCID: PMC8402805 DOI: 10.3390/v13081502] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/17/2022] Open
Abstract
The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.
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Affiliation(s)
- Jacek Furmaga
- Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Marek Kowalczyk
- Institute of Quality Assessment and Processing of Animal Products, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Tomasz Zapolski
- Department of Cardiology, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Olga Furmaga
- Department of Radiology, 424 General Military Hospital, 56403 Thessaloniki, Greece;
| | - Leszek Krakowski
- Department and Clinic of Animal Reproduction, Faculty of Veterinary Medicine, University of Life Sciences, Gleboka 30, 20-612 Lublin, Poland;
| | - Grzegorz Rudzki
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Andrzej Jaroszyński
- Department of Nephrology, Jan Kochanowski University in Kielce, 25-232 Kielce, Poland;
| | - Andrzej Jakubczak
- Institute of Biological Basis of Animal Production, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, 20-950 Lublin, Poland
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