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Banerjee A, Dass D, Mukherjee S, Kaul M, Harshithkumar R, Bagchi P, Mukherjee A. The 'Oma's of the Gammas-Cancerogenesis by γ-Herpesviruses. Viruses 2024; 16:1928. [PMID: 39772235 PMCID: PMC11680331 DOI: 10.3390/v16121928] [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: 11/12/2024] [Revised: 12/10/2024] [Accepted: 12/11/2024] [Indexed: 01/03/2025] Open
Abstract
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis. These viral proteins can modulate several cellular pathways, including the NF-κB and JAK/STAT pathways, which play essential roles in cell survival and inflammation. Epigenetic modifications further contribute to EBV- and KSHV-mediated cancerogenesis. Both EBV and KSHV manipulate host cell DNA methylation, histone modification, and chromatin remodeling, the interplay of which contribute to the elevation of oncogene expression and the silencing of the tumor suppressor genes. Immune factors also play a pivotal role in the development of cancer. The γ-herpesviruses have evolved intricate immune evasion strategies, including the manipulation of the major histocompatibility complex (MHC) and the release of cytokines, allowing infected cells to evade immune detection and destruction. In addition, a compromised immune system, such as in HIV/AIDS patients, significantly increases the risk of cancers associated with EBV and KSHV. This review aims to provide a comprehensive overview of the genetic, epigenetic, and immune mechanisms by which γ-herpesviruses drive cancerogenesis, highlighting key molecular pathways and potential therapeutic targets.
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Affiliation(s)
- Anwesha Banerjee
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
| | - Debashree Dass
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
| | - Soumik Mukherjee
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
| | - Mollina Kaul
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
| | - R. Harshithkumar
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
| | - Parikshit Bagchi
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Anupam Mukherjee
- Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India; (A.B.); (D.D.); (S.M.); (M.K.); (R.H.)
- AcSIR—Academy of Scientific & Innovative Research, Ghaziabad 201002, UP, India
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Wang Y, Ma C, Wang S, Wu H, Chen X, Ma J, Wang L, Qiu HJ, Sun Y. Advances in the immunoescape mechanisms exploited by alphaherpesviruses. Front Microbiol 2024; 15:1392814. [PMID: 38962133 PMCID: PMC11221368 DOI: 10.3389/fmicb.2024.1392814] [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: 02/28/2024] [Accepted: 05/27/2024] [Indexed: 07/05/2024] Open
Abstract
Alphaherpesviruses, categorized as viruses with linear DNA composed of two complementary strands, can potentially to induce diseases in both humans and animals as pathogens. Mature viral particles comprise of a core, capsid, tegument, and envelope. While herpesvirus infection can elicit robust immune and inflammatory reactions in the host, its persistence stems from its prolonged interaction with the host, fostering a diverse array of immunoescape mechanisms. In recent years, significant advancements have been achieved in comprehending the immunoescape tactics employed by alphaherpesviruses, including pseudorabies virus (PRV), herpes simplex virus (HSV), varicella-zoster virus (VZV), feline herpesvirus (FeHV), equine herpesvirus (EHV), and caprine herpesvirus type I (CpHV-1). Researchers have unveiled the intricate adaptive mechanisms existing between viruses and their natural hosts. This review endeavors to illuminate the research advancements concerning the immunoescape mechanisms of alphaherpesviruses by delineating the pertinent proteins and genes involved in virus immunity. It aims to furnish valuable insights for further research on related mechanisms and vaccine development, ultimately contributing to virus control and containment efforts.
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Affiliation(s)
- Yimin Wang
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
| | - Caoyuan Ma
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Shan Wang
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
| | - Hongxia Wu
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Xuanqi Chen
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
| | - Jinyou Ma
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
| | - Lei Wang
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
| | - Hua-Ji Qiu
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Yuan Sun
- Henan Institute of Science and Technology, Xinxiang, China
- Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, China
- State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
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Cinti L, Roberto P, Rossi M, Napoli A, Russo G, Iori AP, Gentile G, Augurusa M, Girmenia C, Antonelli G, Gaeta A. Molecular monitoring of viral infections in immunocompromised patients in a large university hospital in Italy: reflections after thirteen years of real-life activity. Eur J Clin Microbiol Infect Dis 2024; 43:979-989. [PMID: 38517571 PMCID: PMC11108949 DOI: 10.1007/s10096-024-04812-z] [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: 02/12/2024] [Accepted: 03/12/2024] [Indexed: 03/24/2024]
Abstract
PURPOSE This study aimed to investigate the prevalence and viral reactivations of clinical interest in the immunocompromised patient with particular focus on hematologic and solid organ transplant recipients. METHODS Molecular screening data of CMV, EBV, JCV and BKV from 2011 to 2023 were analyzed. This extensive time span allowed the access to more than 100,000 samples from over 20,000 patients treated at Policlinico Umberto I. It was possible to temporally investigate patient attendance patterns, average age distribution, seasonality of infections, and positivity rates of the analyzed viruses. RESULTS Between 2019 and 2022 a significant reduction in organ transplants performed and in the positive molecular detection of EBV, JCV and BKV was observed. Additionally, there has been a noteworthy decrease in CMV reactivations, with a reduction of up to 50% starting in 2019. A remarkable reduction of 39% in the rate of CMV viral reactivation has been also achieved in SOT between 2016 and 2023. CONCLUSION The years following 2019 were profoundly impacted by the COVID-19 pandemic era. This period resulted in a substantial reduction in healthcare services and hospital visits. Furthermore, the introduction of the drug Letermovir in Italy in 2019 demonstrated remarkable efficacy, evidenced by a reduction in CMV reactivations. Additionally, the adoption of a novel clinical approach centered on personalized therapy facilitated improved management of immunocompromised patients.
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Affiliation(s)
- Lilia Cinti
- Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, Roma, 324-00161, Italy
| | - Piergiorgio Roberto
- Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, Roma, 324-00161, Italy.
| | - Matteo Rossi
- Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, Roma, 324-00161, Italy
| | - Anna Napoli
- Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, Roma, 324-00161, Italy
| | - Gianluca Russo
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Roma, Italy
| | - Anna Paola Iori
- Hematology, Department of Hematology, Oncology and Dermatology, AOU Policlinico Umberto I, Sapienza University of Rome, Roma, Italy
| | - Giuseppe Gentile
- Department of Translational and Precision Medicine, Sapienza University Rome, Roma, Italy
- University Hospital "Policlinico Umberto I", Rome, Italy
| | - Maria Augurusa
- University Hospital "Policlinico Umberto I", Rome, Italy
| | - Corrado Girmenia
- Hematology, Department of Hematology, Oncology and Dermatology, AOU Policlinico Umberto I, Sapienza University of Rome, Roma, Italy
| | - Guido Antonelli
- Laboratory of Microbiology and Virology, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, Roma, 324-00161, Italy
- University Hospital "Policlinico Umberto I", Rome, Italy
| | - Aurelia Gaeta
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Roma, Italy
- University Hospital "Policlinico Umberto I", Rome, Italy
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Preiksaitis J, Allen U, Bollard CM, Dharnidharka VR, Dulek DE, Green M, Martinez OM, Metes DM, Michaels MG, Smets F, Chinnock RE, Comoli P, Danziger-Isakov L, Dipchand AI, Esquivel CO, Ferry JA, Gross TG, Hayashi RJ, Höcker B, L'Huillier AG, Marks SD, Mazariegos GV, Squires J, Swerdlow SH, Trappe RU, Visner G, Webber SA, Wilkinson JD, Maecker-Kolhoff B. The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring. Pediatr Transplant 2024; 28:e14471. [PMID: 37294621 DOI: 10.1111/petr.14471] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/10/2022] [Accepted: 01/02/2023] [Indexed: 06/11/2023]
Abstract
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.
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Affiliation(s)
- Jutta Preiksaitis
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Upton Allen
- Division of Infectious Diseases and the Transplant and Regenerative Medicine Center, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Catherine M Bollard
- Center for Cancer and Immunology Research, Children's National Hospital, The George Washington University, Washington, District of Columbia, USA
| | - Vikas R Dharnidharka
- Department of Pediatrics, Division of Pediatric Nephrology, Hypertension & Pheresis, Washington University School of Medicine & St. Louis Children's Hospital, St. Louis, Missouri, USA
| | - Daniel E Dulek
- Division of Pediatric Infectious Diseases, Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Michael Green
- Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Olivia M Martinez
- Department of Surgery and Program in Immunology, Stanford University School of Medicine, Stanford, California, USA
| | - Diana M Metes
- Departments of Surgery and Immunology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Marian G Michaels
- Division of Pediatric Infectious Diseases, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Françoise Smets
- Pediatric Gastroenterology and Hepatology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | | | - Patrizia Comoli
- Cell Factory & Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico, Pavia, Italy
| | - Lara Danziger-Isakov
- Division of Infectious Disease, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - Anne I Dipchand
- Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | | | - Judith A Ferry
- Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Thomas G Gross
- Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Robert J Hayashi
- Division of Pediatric Hematology/Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Britta Höcker
- University Children's Hospital, Pediatrics I, Heidelberg, Germany
| | - Arnaud G L'Huillier
- Faculty of Medicine, Pediatric Infectious Diseases Unit and Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland
| | - Stephen D Marks
- Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, Great Ormond Street Institute of Child Health, London, UK
| | - George Vincent Mazariegos
- Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - James Squires
- Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Steven H Swerdlow
- Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Ralf U Trappe
- Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Bremen, Germany
- Department of Internal Medicine II: Hematology and Oncology, University Medical Centre Schleswig-Holstein, Kiel, Germany
| | - Gary Visner
- Division of Pulmonary Medicine, Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Steven A Webber
- Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA
| | - James D Wilkinson
- Department of Pediatrics, Vanderbilt School of Medicine, Nashville, Tennessee, USA
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Lučiūnaitė A, Dalgėdienė I, Vasiliūnaitė E, Norkienė M, Kučinskaitė-Kodzė I, Žvirblienė A, Gedvilaitė A. Immunogenic Properties and Antigenic Similarity of Virus-like Particles Derived from Human Polyomaviruses. Int J Mol Sci 2023; 24:ijms24054907. [PMID: 36902338 PMCID: PMC10003412 DOI: 10.3390/ijms24054907] [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: 02/07/2023] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Polyomaviruses (PyVs) are highly prevalent in humans and animals. PyVs cause mild illness, however, they can also elicit severe diseases. Some PyVs are potentially zoonotic, such as simian virus 40 (SV40). However, data are still lacking about their biology, infectivity, and host interaction with different PyVs. We investigated the immunogenic properties of virus-like particles (VLPs) derived from viral protein 1 (VP1) of human PyVs. We immunised mice with recombinant HPyV VP1 VLPs mimicking the structure of viruses and compared their immunogenicity and cross-reactivity of antisera using a broad spectrum of VP1 VLPs derived from the PyVs of humans and animals. We demonstrated a strong immunogenicity of studied VLPs and a high degree of antigenic similarity between VP1 VLPs of different PyVs. PyV-specific monoclonal antibodies were generated and applied for investigation of VLPs phagocytosis. This study demonstrated that HPyV VLPs are highly immunogenic and interact with phagocytes. Data on the cross-reactivity of VP1 VLP-specific antisera revealed antigenic similarities among VP1 VLPs of particular human and animal PyVs and suggested possible cross-immunity. As the VP1 capsid protein is the major viral antigen involved in virus-host interaction, an approach based on the use of recombinant VLPs is relevant for studying PyV biology regarding PyV interaction with the host immune system.
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Khalesi Z, Tamrchi V, Razizadeh MH, Letafati A, Moradi P, Habibi A, Habibi N, Heidari J, Noori M, Nahid Samiei M, Azarash Z, Hoseini M, Saadati H, Bahavar A, Farajzade M, Saeb S, Hadadi M, Sorouri Majd M, Mothlaghzadeh S, Fazli P, Asgari K, Kiani SJ, Ghorbani S. Association between human herpesviruses and multiple sclerosis: A systematic review and meta-analysis. Microb Pathog 2023; 177:106031. [PMID: 36775211 DOI: 10.1016/j.micpath.2023.106031] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/01/2023] [Accepted: 02/09/2023] [Indexed: 02/12/2023]
Abstract
AIM The aim of this study was to investigate the prevalence and potential association between infection with different herpes viruses and multiple sclerosis (MS). METHODS A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, Odds ratio (OR), and corresponding 95% Confidence interval (CI) were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14. RESULTS One hundred and thirty-four articles (289 datasets) were included in the meta-analysis, 128 (245 datasets) of which were case/control and the rest were cross-sectional. The pooled prevalence of all human herpes viruses among MS patients was 50% (95% CI: 45-55%; I2 = 96.91%). In subgroup analysis, the pooled prevalence of Herpes simplex virus (HSV), Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpes virus 8 (HHV-8) was 32%, 52%, 74%, 41%, 39% 28%, and 28%, respectively. An association was found between infection with human herpes viruses and MS [summary OR 2.07 (95% CI (1.80-2.37); I2 = 80%)]. CONCLUSION The results of the present study showed that EBV, VZV, and HHV-6 infection are associated with multiple sclerosis and can be considered as potential risk factors for MS. Although the exact molecular mechanism of the role of herpes viruses in the development of MS is still unknown, it seems that molecular mimicry, the release of autoreactive antibodies, and inflammation in the CNS following viral infection can be important factors in the induction of MS.
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Affiliation(s)
- Zohreh Khalesi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahid Tamrchi
- Department of Microbiology of Golestan University of Medical Sciences, Golesatn, Iran
| | | | - Arash Letafati
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouya Moradi
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Arezoo Habibi
- Department of Biochemistry, Faculty of Basic Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
| | - Negar Habibi
- Department of Biochemistry, Faculty of Basic Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
| | - Jafar Heidari
- Department of Microbiology, Faculty of Veterinary Medical, Urmia University, Urmia, West Azarbaijan, Iran
| | - Maryam Noori
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahboubeh Nahid Samiei
- Faculty of Medicine, Islamic Azad University, Shiraz University of Medical Science, Shiraz, Iran
| | - Ziba Azarash
- Department of Virology, Faculty of Medicine, Tarbiat Modares University, Tehran, Iran
| | - Mahdiyeh Hoseini
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hassan Saadati
- Department of Epidemiology and Biostatistics, School of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Atefeh Bahavar
- Department of Microbiology of Golestan University of Medical Sciences, Golesatn, Iran
| | - Maryam Farajzade
- Faculty of Paramedicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Sepideh Saeb
- Medical Virology Student, Department of Virology, Lorestan University of Medical Science, Khorramabad, Iran
| | - Mohammad Hadadi
- Department of Microbiology, Faculty of Sciences, Karaj Branch, Islamic Azad University, Karaj, Iran
| | - Mahdieh Sorouri Majd
- Department of Medical Sciences, Faculty of Paramedicl, Qom Branch, Islamic Azad University, Qom, Iran
| | - Saeed Mothlaghzadeh
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Paria Fazli
- Department of Virology, Faculty of Medicine, Hamadan University of Medical Science, Hamadan, Iran
| | - Katayoon Asgari
- Department of Clinical Biochemistry, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Seyed Jalal Kiani
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Saied Ghorbani
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Flores-Hidalgo A, Thompson S, Paquette D. Long-standing ulcer in mandibular gingiva in a patient with polymyalgia rheumatica. Oral Surg Oral Med Oral Pathol Oral Radiol 2023; 135:169-174. [PMID: 36229368 DOI: 10.1016/j.oooo.2022.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/11/2022] [Accepted: 07/14/2022] [Indexed: 10/17/2022]
Affiliation(s)
- Andres Flores-Hidalgo
- Division of Oral and Maxillofacial Pathology, East Carolina University, Greenville, NC, USA; Department of Surgical Sciences, East Carolina University School of Dental Medicine, Greenville, NC, USA.
| | - Stevan Thompson
- Division of Oral and Maxillofacial Surgery, East Carolina University, Greenville, NC, USA; Department of Surgical Sciences, East Carolina University School of Dental Medicine, Greenville, NC, USA
| | - David Paquette
- Department of Surgical Sciences, East Carolina University School of Dental Medicine, Greenville, NC, USA
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Prezioso C, Pietropaolo V, Moens U, Ciotti M. JC polyomavirus: a short review of its biology, its association with progressive multifocal leukoencephalopathy, and the diagnostic value of different methods to manifest its activity or presence. Expert Rev Mol Diagn 2023; 23:143-157. [PMID: 36786077 DOI: 10.1080/14737159.2023.2179394] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Abstract
INTRODUCTION JC polyomavirus is the causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease resulting from the lytic infection of oligodendrocytes that may develop in immunosuppressed individuals: HIV1 infected or individuals under immunosuppressive therapies. Understanding the biology of JCPyV is necessary for a proper patient management, the development of diagnostic tests, and risk stratification. AREAS COVERED The review covers different areas of expertise including the genomic characterization of JCPyV strains detected in different body compartments (urine, plasma, and cerebrospinal fluid) of PML patients, viral mutations, molecular diagnostics, viral miRNAs, and disease. EXPERT OPINION The implementation of molecular biology techniques improved our understanding of JCPyV biology. Deep sequencing analysis of viral genomes revealed the presence of viral quasispecies in the cerebrospinal fluid of PML patients characterized by noncoding control region rearrangements and VP1 mutations. These neurotropic JCPyV variants present enhanced replication and an altered cell tropism that contribute to PML development. Monitoring these variants may be relevant for the identification of patients at risk of PML. Multiplex realtime PCR targeting both the LTAg and the archetype NCCR could be used to identify them. Failure to amplify NCCR should indicate the presence of a JCPyV prototype speeding up the diagnostic process.
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Affiliation(s)
- Carla Prezioso
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome Rome, Italy.,IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies Rome, Italy
| | - Valeria Pietropaolo
- Department of Public Health and Infectious Diseases, "Sapienza" University of Rome Rome, Italy
| | - Ugo Moens
- Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway Tromsø, Norway
| | - Marco Ciotti
- Virology Unit, Polyclinic Tor Vergata Rome, Italy
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Santiago-Rodriguez TM, Hollister EB. Viral Metagenomics as a Tool to Track Sources of Fecal Contamination: A One Health Approach. Viruses 2023; 15:236. [PMID: 36680277 PMCID: PMC9863393 DOI: 10.3390/v15010236] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/10/2023] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
The One Health framework recognizes that human, animal, and environmental health are linked and highly interdependent. Fecal contamination of water, soil, foodstuff, and air may impact many aspects of One Health, and culture, PCR-based, and sequencing methods are utilized in the detection of fecal contamination to determine source, load, and risk to inform targeted mitigation strategies. Viruses, particularly, have been considered as fecal contamination indicators given the narrow host range many exhibit and their association with other biological contaminants. Culture- and molecular-based methods are considered the gold-standards for virus detection and for determining specific sources of fecal contamination via viral indicators. However, viral metagenomics is also being considered as a tool for tracking sources of fecal contamination. In the present review, studies tracking potential sources of fecal contamination in freshwaters, marine waters, foodstuff, soil, and air using viral metagenomics are discussed to highlight the potential of viral metagenomics for optimizing fecal source tracking. Limitations of the use of viral metagenomics to track fecal contamination sources, including sample processing, nucleic acid recovery, sequencing depth, and bioinformatics are also discussed. Finally, the present review discusses the potential of viral metagenomics as part of the toolbox of methods in a One Health approach.
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10
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Dias MHF, Guimarães LFF, Barcelos MG, Moreira EUM, do Nascimento MFA, de Souza TN, Pires CV, Monteiro TAF, Middeldorp JM, Soares IS, Fontes CJF, Ntumngia FB, Adams JH, Kano FS, Carvalho LH. Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response. PLoS Negl Trop Dis 2022; 16:e0010305. [PMID: 35921373 PMCID: PMC9377613 DOI: 10.1371/journal.pntd.0010305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 08/15/2022] [Accepted: 07/22/2022] [Indexed: 11/18/2022] Open
Abstract
Background
The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt’s Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite.
Methodology/Principal findings
The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission.
Conclusions/Significance
In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.
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Affiliation(s)
| | | | | | | | | | - Taís N. de Souza
- Instituto René Rachou/FIOCRUZ Minas, Belo Horizonte, Minas Gerais, Brazil
| | - Camilla V. Pires
- Center for Global Health and Infectious Diseases Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America
| | - Talita A. F. Monteiro
- Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde (IEC/SVS/MS), Belém, Pará, Brazil
| | - Jaap M. Middeldorp
- Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands
| | - Irene S. Soares
- Faculdade de Ciências Farmacêuticas, Universidade de São Paulo (USP), São Paulo, Brazil
| | - Cor J. F. Fontes
- Julio Müller School Hospital, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, Mato Grosso, Brazil
| | - Francis B. Ntumngia
- Center for Global Health and Infectious Diseases Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America
| | - John H. Adams
- Center for Global Health and Infectious Diseases Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America
| | - Flora S. Kano
- Instituto René Rachou/FIOCRUZ Minas, Belo Horizonte, Minas Gerais, Brazil
| | - Luzia H. Carvalho
- Instituto René Rachou/FIOCRUZ Minas, Belo Horizonte, Minas Gerais, Brazil
- * E-mail:
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11
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He YQ, Zhou T, Yang DW, Jia YJ, Yuan LL, Zhang WL, Wang TM, Liao Y, Xue WQ, Zhang JB, Zheng XH, Li XZ, Zhang PF, Zhang SD, Hu YZ, Wang F, Cho WC, Ma J, Sun Y, Jia WH. Prognostic Value of Oral Epstein–Barr Virus DNA Load in Locoregionally Advanced Nasopharyngeal Carcinoma. Front Mol Biosci 2022; 8:757644. [PMID: 35096963 PMCID: PMC8793774 DOI: 10.3389/fmolb.2021.757644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 12/15/2021] [Indexed: 12/24/2022] Open
Abstract
Background: Plasma Epstein–Barr virus (EBV) DNA load has been widely used for nasopharyngeal carcinoma (NPC) prognostic risk stratification. However, oral EBV DNA load, a non-invasive biomarker that reflects the EBV lytic replication activity, has not been evaluated for its prognostic value in NPC yet. Methods: A total number of 1,194 locoregionally advanced NPC (LA-NPC) patients from south China were included from a prospective observational cohort (GARTC) with a median follow-up of 107.3 months. Pretreatment or mid-treatment mouthwashes were collected for EBV DNA detection by quantitative polymerase chain reaction (qPCR). The difference of pre- and mid-treatment oral EBV DNA load was tested by the Wilcoxon signed-rank test. The associations of oral EBV DNA load with overall survival (OS), progression-free survival (PFS), distant metastasis–free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed using the log-rank test and multivariate Cox regression. Results: The high level of the oral EBV DNA load (>2,100 copies/mL) was independently associated with worse OS (HR = 1.45, 95% CI: 1.20–1.74, p < 0.001), PFS (HR = 1.38, 95% CI: 1.16–1.65, p < 0.001), DMFS (HR = 1.66, 95% CI: 1.25–2.21, p = 0.001), and LRFS (HR = 1.43, 95% CI: 1.05–1.96, p = 0.023). Similar and robust associations between oral EBV DNA load and prognosis were observed for patients in both the pretreatment and mid-treatment stages. The detection rate (71.7 vs. 48.6%, p < 0.001) and the median load of oral EBV DNA (13,368 vs. 382 copies/mL, p < 0.001) for patients in the pretreatment stage were significantly higher than those in the mid-treatment stage. The combination of the oral EBV DNA load and TNM staging provided a more precise risk stratification for the LA-NPC patients. Conclusion: Oral EBV DNA load was an alternative non-invasive predictor of prognosis and may facilitate risk stratification for the LA-NPC patients.
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Affiliation(s)
- Yong-Qiao He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ting Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Da-Wei Yang
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yi-Jing Jia
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Lei-Lei Yuan
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wen-Li Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tong-Min Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Liao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Qiong Xue
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiang-Bo Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Hui Zheng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xi-Zhao Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Pei-Fen Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shao-Dan Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ye-Zhu Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
| | - Jun Ma
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying Sun
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wei-Hua Jia
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- Biobank of Sun Yat-sen University Cancer Center, Guangzhou, China
- School of Public Health, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Wei-Hua Jia,
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12
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Blazquez-Navarro A, Dang-Heine C, Wehler P, Roch T, Bauer C, Neumann S, Blazquez-Navarro R, Kurchenko A, Wolk K, Sabat R, Westhoff TH, Olek S, Thomusch O, Seitz H, Reinke P, Hugo C, Sawitzki B, Or-Guil M, Babel N. Risk factors for Epstein-Barr virus reactivation after renal transplantation: Results of a large, multi-centre study. Transpl Int 2021; 34:1680-1688. [PMID: 34448272 DOI: 10.1111/tri.13982] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 07/15/2021] [Accepted: 07/15/2021] [Indexed: 01/02/2023]
Abstract
Epstein-Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.
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Affiliation(s)
- Arturo Blazquez-Navarro
- Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.,Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Center for Translational Medicine, Universitätsklinikum der Ruhr-Universität Bochum, Medizinische Klinik I, Herne, Germany
| | - Chantip Dang-Heine
- Clinical Study Center (CSC), Berlin Institute of Health, and Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Patrizia Wehler
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Center for Translational Medicine, Universitätsklinikum der Ruhr-Universität Bochum, Medizinische Klinik I, Herne, Germany
| | - Toralf Roch
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Center for Translational Medicine, Universitätsklinikum der Ruhr-Universität Bochum, Medizinische Klinik I, Herne, Germany
| | | | | | | | - Andriy Kurchenko
- Department of Clinical Immunology and Allergology, Bogolomets National Medical University, Kiev, Ukraine
| | - Kerstin Wolk
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Psoriasis Research and Treatment Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Robert Sabat
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Psoriasis Research and Treatment Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Timm H Westhoff
- Center for Translational Medicine, Universitätsklinikum der Ruhr-Universität Bochum, Medizinische Klinik I, Herne, Germany
| | - Sven Olek
- Ivana Türbachova Laboratory for Epigenetics, Epiontis GmbH, Precision for Medicine Group, Berlin, Germany
| | - Oliver Thomusch
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Harald Seitz
- Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics und Bioprocesses, Leipzig, Germany
| | - Petra Reinke
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT), Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Christian Hugo
- Universitätsklinikum Carl Gustav Carus, Medizinische Klinik III - Bereich Nephrologie, Dresden, Germany
| | - Birgit Sawitzki
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Michal Or-Guil
- Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.,Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Nina Babel
- Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Center for Translational Medicine, Universitätsklinikum der Ruhr-Universität Bochum, Medizinische Klinik I, Herne, Germany
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13
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Epstein-Barr Virus Lytic Replication Induces ACE2 Expression and Enhances SARS-CoV-2 Pseudotyped Virus Entry in Epithelial Cells. J Virol 2021; 95:e0019221. [PMID: 33853968 DOI: 10.1128/jvi.00192-21] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Understanding factors that affect the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is central to combatting coronavirus disease 2019 (COVID-19). The virus surface spike protein of SARS-CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We found that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using vesicular stomatitis virus (VSV) particles pseudotyped with the SARS-CoV-2 spike protein, we showed that lytic EBV replication enhances ACE2-dependent SARS-CoV-2 pseudovirus entry. We found that the ACE2 promoter contains response elements for Zta, an EBV transcriptional activator that is essential for EBV entry into the lytic cycle of replication. Zta preferentially acts on methylated promoters, allowing it to reactivate epigenetically silenced EBV promoters from latency. By using promoter assays, we showed that Zta directly activates methylated ACE2 promoters. Infection of normal oral keratinocytes with EBV leads to lytic replication in some of the infected cells, induces ACE2 expression, and enhances SARS-CoV-2 pseudovirus entry. These data suggest that subclinical EBV replication and lytic gene expression in epithelial cells, which is ubiquitous in the human population, may enhance the efficiency and extent of SARS-CoV-2 infection of epithelial cells by transcriptionally activating ACE2 and increasing its cell surface expression. IMPORTANCE SARS-CoV-2, the coronavirus responsible for COVID-19, has caused a pandemic leading to millions of infections and deaths worldwide. Identifying the factors governing susceptibility to SARS-CoV-2 is important in order to develop strategies to prevent SARS-CoV-2 infection. We show that Epstein-Barr virus, which infects and persists in >90% of adult humans, increases susceptibility of epithelial cells to infection by SARS-CoV-2. EBV, when it reactivates from latency or infects epithelial cells, increases expression of ACE2, the cellular receptor for SARS-CoV-2, enhancing infection by SARS-CoV-2. Inhibiting EBV replication with antivirals may therefore decrease susceptibility to SARS-CoV-2 infection.
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14
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Speidel JD, Gilles S, Steer B, Vafadari B, Rauer D, Traidl‐Hoffmann C, Adler H. Pollen induces reactivation of latent herpesvirus and differentially affects infected and uninfected murine macrophages. Allergy 2021; 76:1539-1542. [PMID: 32905616 DOI: 10.1111/all.14587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/24/2020] [Indexed: 11/30/2022]
Affiliation(s)
- Jan Dominik Speidel
- Research Unit Lung Repair and Regeneration Comprehensive Pneumology Center Helmholtz Zentrum München ‐ German Research Center for Environmental Health (GmbH); Member of the German Center of Lung Research (DZL) Munich Germany
| | - Stefanie Gilles
- Chair and Institute of Environmental Medicine UNIKA‐TTechnical University of Munich and Helmholtz Zentrum München Augsburg Germany
| | - Beatrix Steer
- Research Unit Lung Repair and Regeneration Comprehensive Pneumology Center Helmholtz Zentrum München ‐ German Research Center for Environmental Health (GmbH); Member of the German Center of Lung Research (DZL) Munich Germany
| | - Behnam Vafadari
- Chair and Institute of Environmental Medicine UNIKA‐TTechnical University of Munich and Helmholtz Zentrum München Augsburg Germany
| | - Denise Rauer
- Chair and Institute of Environmental Medicine UNIKA‐TTechnical University of Munich and Helmholtz Zentrum München Augsburg Germany
| | - Claudia Traidl‐Hoffmann
- Chair and Institute of Environmental Medicine UNIKA‐TTechnical University of Munich and Helmholtz Zentrum München Augsburg Germany
| | - Heiko Adler
- Research Unit Lung Repair and Regeneration Comprehensive Pneumology Center Helmholtz Zentrum München ‐ German Research Center for Environmental Health (GmbH); Member of the German Center of Lung Research (DZL) Munich Germany
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15
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The Epstein-Barr Virus Major Tegument Protein BNRF1 Is a Common Target of Cytotoxic CD4 + T Cells. J Virol 2020; 94:JVI.00284-20. [PMID: 32461311 DOI: 10.1128/jvi.00284-20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/18/2020] [Indexed: 01/14/2023] Open
Abstract
Cellular immunotherapy is a proven approach against Epstein-Barr virus (EBV)-driven lymphoproliferation in recipients of hematopoietic stem cells. Extending the applicability and improving the response rates of such therapy demands improving the knowledge base. We studied 23 healthy donors for specific CD4+ T cell responses against the viral tegument protein BNRF1 and found such T cells in all seropositive donors, establishing BNRF1 as an important immune target in EBV. We identified 18 novel immune epitopes from BNRF1, all of them generated by natural processing of the full-length protein from virus-transformed lymphoblastoid cell lines (LCL). BNRF1-specific CD4+ T cells were measured directly ex vivo by a cytokine-based method, thus providing a tool to study the interaction between immunity and infection in health and disease. T cells of the cytotoxic Th1 type inhibited the proliferation of autologous LCL as well as virus-driven transformation. We infer that they are important in limiting reactivations to subclinical levels during health and reducing virus propagation during disease. The information obtained from this work will feed into data sets that are indispensable in the design of patient-tailored immunotherapeutic approaches, thereby enabling the stride toward broader application of T cell therapy and improving clinical response rates.IMPORTANCE Epstein-Barr virus is carried by most humans and can cause life-threatening diseases. Virus-specific T cells have been used in different clinical settings with variable success rates. One way to improve immunotherapy is to better suit T cell generation protocols to viral targets available in different diseases. BNRF1 is present in viral particles and therefore likely available as a target for T cells in diseases with virus amplification. Here, we studied healthy Epstein-Barr virus (EBV) carriers for BNRF1 immunogenicity and report our results indicating BNRF1 to be a dominant target of the EBV-specific CD4+ T cell response. BNRF1-specific CD4+ T cells were found to be cytotoxic and capable of limiting EBV-driven B cell transformation in vitro The findings of this work contribute to forwarding our understanding of host-virus interactions during health and disease and are expected to find direct application in the generation of specific T cells for immunotherapy.
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16
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Dall Agnol AM, Leme RA, Suphoronski SA, Oliveira TES, Possatti F, Saporiti V, Headley SA, Alfieri AA, Alfieri AF. Porcine lymphotropic herpesvirus DNA detection in multiple organs of pigs in Brazil. Braz J Microbiol 2020; 51:2145-2152. [PMID: 32638274 DOI: 10.1007/s42770-020-00335-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 07/01/2020] [Indexed: 11/28/2022] Open
Abstract
We investigated the porcine lymphotropic herpesvirus (PLHV) DNA presence in multiple organs of pigs. Biological samples (n = 136) included tissue fragments of the central nervous system, heart, kidney, liver, lungs, spleen, urinary bladder, and urine. Sixty-eight (50%) organs were PLHV DNA-positive. None of the urine samples were detected with the virus genome. Although the presence of the PLHV DNA in the urinary bladder and kidney has been detected, it was not possible to show whether urine can be considered an effective route of virus shedding. This study warns to the risk of PLHV zoonotic transmission by xenotransplantation of tissues of porcine origin.
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Affiliation(s)
- Alais M Dall Agnol
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil.,Multi-User Animal Health Laboratory, Molecular Biology Unit, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Raquel A Leme
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil.,Multi-User Animal Health Laboratory, Molecular Biology Unit, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Suelen A Suphoronski
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil
| | - Thalita E S Oliveira
- Laboratory of Animal Pathology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Flávia Possatti
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil
| | - Viviane Saporiti
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil
| | - Selwyn A Headley
- Laboratory of Animal Pathology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
| | - Amauri Alcindo Alfieri
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil. .,Multi-User Animal Health Laboratory, Molecular Biology Unit, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
| | - Alice Fernandes Alfieri
- Laboratory of Animal Virology, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid - Campus Universitário. CEP 86057-970, PO Box 10011, Londrina, Paraná, Brazil.,Multi-User Animal Health Laboratory, Molecular Biology Unit, Department of Veterinary Preventive Medicine, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
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17
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Soldan SS, Lieberman PM. Epstein-Barr Virus Infection in the Development of Neurological Disorders. ACTA ACUST UNITED AC 2020; 32:35-52. [PMID: 33897799 DOI: 10.1016/j.ddmod.2020.01.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Epstein-Barr Virus (EBV) is a ubiquitous human herpesvirus that contributes to the etiology of diverse human cancers and auto-immune diseases. EBV establishes a relatively benign, long-term latent infection in over 90 percent of the adult population. Yet, it also increases risk for certain cancers and auto-immune disorders depending on complex viral, host, and environmental factors that are only partly understood. EBV latent infection is found predominantly in memory B-cells, but the natural infection cycle and pathological aberrations enable EBV to infect numerous other cell types, including oral, nasopharyngeal, and gastric epithelia, B-, T-, and NK-lymphoid cells, myocytes, adipocytes, astrocytes, and neurons. EBV infected cells, free virus, and gene products can also be found in the CNS. In addition to the direct effects of EBV on infected cells and tissue, the effect of chronic EBV infection on the immune system is also thought to contribute to pathogenesis, especially auto-immune disease. Here, we review properties of EBV infection that may shed light on its potential pathogenic role in neurological disorders.
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18
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Dynamic expression of JC virus in urine and its relationship to serostatus. Mult Scler Relat Disord 2020; 41:101972. [PMID: 32135498 DOI: 10.1016/j.msard.2020.101972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 01/23/2020] [Accepted: 01/27/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND There is limited information regarding the daily shedding of JC virus (JCV) in urine and its correlation with serum JCV antibody levels. METHODS The dynamic expression of JCV in urine and its correlation with JCV antibody status in patients receiving disease modifying therapy for multiple sclerosis were examined in a longitudinal case-control study. JCV antibody index levels were determined using a two-step ELISA (Stratify). JCV shedding in urine samples was determined by quantitative PCR during two 30-day study periods separated by intervals of at least 6 months. RESULTS Of 42 study subjects (57% female; ages 22-56, average age 39.6 years), 27 (64.3%) were JCV antibody positive (index >0.40) at initial urine collection. Twelve seropositive subjects (44.4%) had detectable JCV in their urine with values ranging from 290 to 5.08 × 108 copies/mL. Daily viral shedding in these patients remained fairly constant throughout the study. Urinary JCV shedding was not detected in any JCV antibody index negative or indeterminate subject. In JCV urinary shedders, the average JCV antibody index was 2.69 (range 1.67-3.57). The average anti-JCV antibody index for the remaining JCV seropositive individuals without viral urinary shedding was 1.35 (range 0.46-3.91). CONCLUSION MS patients displayed a consistent pattern of JCV shedding over days and months in which higher levels of viruria appeared to have driven higher levels of JCV antibody index. The findings provide additional insights into the dynamic expression of JCV and host response; however, studies in larger populations and of longer duration will be needed to determine their significance to the development of progressive multifocal leukoencephalopathy (PML).
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19
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He YQ, Liao XY, Xue WQ, Xu YF, Xu FH, Li FF, Li XZ, Zhang JB, Wang TM, Wang F, Yu HL, Feng QS, Chen LZ, Cao SM, Liu Q, Mu J, Jia WH. Association Between Environmental Factors and Oral Epstein-Barr Virus DNA Loads: A Multicenter Cross-sectional Study in China. J Infect Dis 2019; 219:400-409. [PMID: 30307559 DOI: 10.1093/infdis/jiy542] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 10/08/2018] [Indexed: 12/14/2022] Open
Abstract
Background Oral Epstein-Barr virus (EBV) status reflects host EBV activity and potentially links to EBV-associated diseases, however, factors influencing oral EBV loads or reactivation, such as environmental exposures or host factors, are not fully understood. Methods A 2-stage, multicenter, cross-sectional study of 6558 subjects from 21 administrative cities of southern China and 3 populations from representative geographical areas in China (referred to as the south, north, and northeastern populations) was performed. The relationships between demographical factors and environmental exposures to EBV loads were analyzed by logistic regression models. Results Current smoking, with a dose-response effect, was found to be strongly associated with higher oral EBV loads in the pooled data, with an odds ratio of 1.58 (95% confidence interval, 1.39-1.79), as well as in each of the separate populations. The odds ratio increased to 3.06 when current smokers in southern China were compared to never smokers in northern China. Additionally, higher oral EBV loads tended to be detected in older participants, male participants, and participants in southern China. Conclusions This study provided evidence linking the effect of host-environmental factors, particularly smoking, to oral EBV activity. It could strengthen our understanding of the possible causal roles of EBV-related diseases, which may help to prevent or mitigate EBV-associated diseases.
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Affiliation(s)
- Yong-Qiao He
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Xiao-Yu Liao
- Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing
| | - Wen-Qiong Xue
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Ya-Fei Xu
- Shenzhen University Health Science Center, Shenzhen, China
| | - Feng-Hua Xu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Fang-Fang Li
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Xi-Zhao Li
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Jiang-Bo Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Tong-Min Wang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Fang Wang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Huan-Lin Yu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Qi-Sheng Feng
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Li-Zhen Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Su-Mei Cao
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Qing Liu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou
| | - Jianbing Mu
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland
| | - Wei-Hua Jia
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou.,Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou.,School of Public Health, Sun Yat-Sen University, Guangzhou.,Cancer Center of Guangzhou Medical University, Guangzhou
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20
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Kamminga S, van der Meijden E, de Brouwer C, Feltkamp M, Zaaijer H. Prevalence of DNA of fourteen human polyomaviruses determined in blood donors. Transfusion 2019; 59:3689-3697. [PMID: 31633816 PMCID: PMC6916541 DOI: 10.1111/trf.15557] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 09/24/2019] [Accepted: 09/24/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Human polyomaviruses (HPyVs), like herpesviruses, cause persistent infection in a large part of the population. In immunocompromised and elderly patients, PyVs cause severe diseases such as nephropathy (BK polyomavirus [BKPyV]), progressive multifocal leukoencephalopathy (JC polyomavirus [JCPyV]), and skin cancer (Merkel cell polyomavirus [MCPyV]). Like cytomegalovirus, donor‐derived PyV can cause disease in kidney transplant recipients. Possibly blood components transmit PyVs as well. To study this possibility, as a first step we determined the presence of PyV DNA in Dutch blood donations. STUDY DESIGN AND METHODS Blood donor serum samples (n = 1016) were analyzed for the presence of DNA of 14 HPyVs using HPyV species‐specific quantitative polymerase chain reaction (PCR) procedures. PCR‐positive samples were subjected to confirmation by sequencing. Individual PCR findings were compared with the previously reported PyV serostatus. RESULTS MC polyomavirus DNA was detected in 39 donors (3.8%), JCPyV and TS polyomavirus (TSPyV) DNA in five donors (both 0.5%), and HPyV9 DNA in four donors (0.4%). BKPyV, WU polyomavirus (WUPyV), HPyV6, MW polyomavirus (MWPyV), and LI polyomavirus (LIPyV) DNA was detected in one or two donors. Amplicon sequencing confirmed the expected product for BKPyV, JCPyV, WUPyV, MCPyV, HPyV6, TSPyV, MWPyV, HPyV9, and LIPyV. For JCPyV a significant association was observed between detection of viral DNA and the level of specific IgG antibodies. CONCLUSION In 5.4% of Dutch blood donors PyV DNA was detected, including DNA from pathogenic PyVs such as JCPyV. As a next step, the infectivity of PyV in donor blood and transmission via blood components to immunocompromised recipients should be investigated.
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Affiliation(s)
- Sergio Kamminga
- Department of Blood-borne Infections, Sanquin Research, Amsterdam, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Els van der Meijden
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Caroline de Brouwer
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Mariet Feltkamp
- Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Hans Zaaijer
- Department of Blood-borne Infections, Sanquin Research, Amsterdam, Netherlands
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21
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Della Chiesa M, De Maria A, Muccio L, Bozzano F, Sivori S, Moretta L. Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation. Front Microbiol 2019; 10:2297. [PMID: 31636622 PMCID: PMC6788305 DOI: 10.3389/fmicb.2019.02297] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 09/20/2019] [Indexed: 12/01/2022] Open
Abstract
NK cells contribute to early defenses against viruses through their inborn abilities that include sensing of PAMPs and inflammatory signals such as cytokines or chemokines, recognition, and killing of infected cells through activating surface receptors engagement. Moreover, they support adaptive responses via Ab-dependent mechanisms, triggered by CD16, and DC editing. Their fundamental role in anti-viral responses has been unveiled in patients with NK cell deficiencies suffering from severe Herpesvirus infections. Notably, these infections, often occurring as primary infections early in life, can be efficiently cleared by NK, T, and B cells in healthy hosts. Herpesviruses however, generate a complicated balance with the host immune system through their latency cycle moving between immune control and viral reactivation. This lifelong challenge has contributed to the development of numerous evasion mechanisms by Herpesviruses, many of which devoted to elude NK cell surveillance from viral reactivations rather than primary infections. This delicate equilibrium can be altered in proportions of healthy individuals promoting virus reactivation and, more often, in immunocompromised subjects. However, the constant stimulus provided by virus-host interplay has also favored NK-cell adaptation to Herpesviruses. During anti-HCMV responses, NK cells can reshape their receptor repertoire and function, through epigenetic remodeling, and acquire adaptive traits such as longevity and clonal expansion abilities. The major mechanisms of recognition and effector responses employed by NK cells against Herpesviruses, related to their genomic organization will be addressed, including those allowing NK cells to generate memory-like responses. In addition, the mechanisms underlying virus reactivation or control will be discussed.
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Affiliation(s)
- Mariella Della Chiesa
- Department of Experimental Medicine (DIMES), School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy.,Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
| | - Andrea De Maria
- Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.,Department of Health Sciences (DISSAL), School of Medical and Pharmaceutical Sciences University of Genoa, Genoa, Italy.,Clinica Malattie Infettive, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Letizia Muccio
- Department of Experimental Medicine (DIMES), School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy
| | - Federica Bozzano
- Laboratory of Tumor Immunology, Department of Immunology, IRCCS Ospedale Bambino Gesù, Rome, Italy
| | - Simona Sivori
- Department of Experimental Medicine (DIMES), School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy.,Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
| | - Lorenzo Moretta
- Laboratory of Tumor Immunology, Department of Immunology, IRCCS Ospedale Bambino Gesù, Rome, Italy
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22
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Liu Z, Coghill AE, Pfeiffer RM, Proietti C, Hsu WL, Chien YC, Lekieffre L, Krause L, Yu KJ, Lou PJ, Wang CP, Mulvenna J, Middeldorp JM, Bethony J, Chen CJ, Doolan DL, Hildesheim A. Patterns of Interindividual Variability in the Antibody Repertoire Targeting Proteins Across the Epstein-Barr Virus Proteome. J Infect Dis 2019; 217:1923-1931. [PMID: 29509907 DOI: 10.1093/infdis/jiy122] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 03/01/2018] [Indexed: 12/25/2022] Open
Abstract
Background Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk. Methods We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses. Results Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10-46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test-combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk. Conclusions These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.
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Affiliation(s)
- Zhiwei Liu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Anna E Coghill
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Carla Proietti
- QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia.,Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
| | - Wan-Lun Hsu
- Genomics Research Center, Academia Sinica, Taipei.,Graduate Institute of Epidemiology and Prevention Medicine, College of Public Health, National Taiwan University, Taipei
| | - Yin-Chu Chien
- Genomics Research Center, Academia Sinica, Taipei.,National Institute of Cancer Research, National Health Research Institute, Miaoli, Taiwan
| | - Lea Lekieffre
- QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia
| | - Lutz Krause
- QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Pei-Jen Lou
- Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei
| | - Cheng-Ping Wang
- Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei
| | - Jason Mulvenna
- QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia
| | - Jaap M Middeldorp
- Department of Pathology, VU University Medical Center, Amsterdam, Netherlands
| | - Jeff Bethony
- Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Washington, D. C
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei.,Graduate Institute of Epidemiology and Prevention Medicine, College of Public Health, National Taiwan University, Taipei
| | - Denise L Doolan
- QIMR Berghofer Medical Research Institute, Brisbane, Cairns, Australia.,Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
| | - Allan Hildesheim
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
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23
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Kumari K, Pradeep I, Kakkar A, Dinda AK, Seth A, Nayak B, Singh G. BK polyomavirus and urothelial carcinoma: Experience at a tertiary care centre in India with review of literature. Ann Diagn Pathol 2019; 40:77-80. [PMID: 31075667 DOI: 10.1016/j.anndiagpath.2019.04.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/12/2019] [Accepted: 04/22/2019] [Indexed: 11/26/2022]
Abstract
INTRODUCTION BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma. MATERIAL AND METHODS Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal). RESULTS Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining. CONCLUSIONS This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.
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Affiliation(s)
- Kalpana Kumari
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Immanuel Pradeep
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Aanchal Kakkar
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Kumar Dinda
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Amlesh Seth
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | - B Nayak
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | - Geetika Singh
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
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24
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Levican J, Levican A, Ampuero M, Gaggero A. JC polyomavirus circulation in one-year surveillance in wastewater in Santiago, Chile. INFECTION GENETICS AND EVOLUTION 2019; 71:151-158. [PMID: 30905776 DOI: 10.1016/j.meegid.2019.03.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/19/2019] [Accepted: 03/20/2019] [Indexed: 11/27/2022]
Abstract
Human polyomavirus JC (JCPyV) is a widely distributed viral agent and because it high resistance against environmental conditions it is frequently recovered from diverse sources of water and is considered a good marker for human pollution. Phylogenetic analysis of JCPyV isolated in different part of the world has revealed 7 genotypes, which have been associated with specific populations or ethnics groups. This feature has been used to trace pre-historic and historic human migration patterns across the world. Although there are many reports describing genotypes distribution around the world, data on JCPyV genotypes in the southernmost areas of South America are scarce. The goal of this study is to detect and characterize the JCPyV that circulates in Santiago, Chile using sewage samples from wastewater treatment plants (WWTP). Sewage samples were obtained monthly during 1 year from three WWTPs which together process about 80% of wastewater generated in the city of Santiago, Chile. Our results show that JCPyV profusely circulates in Santiago, Chile, because it was detected in 80.56% of the samples, reinforcing the use of JCPyV as a feasible marker to assess human environmental pollution. JCPyV was detected in high frequency in influents and effluents samples, with the largest WWTPs showing the highest percentage of detection and viral loads. In the phylogenetic analysis the Chilean sequences clustered mainly with genotype 2A (Asian genotype). This is similar to that previously reported from Buenos Aires, Argentina and divergent to data from Brazil, where the circulation of European subtypes 1 and 4 and African subtypes 3 and 6 has been described.
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Affiliation(s)
- Jorge Levican
- Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Arturo Levican
- Tecnología Médica, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
| | - Manuel Ampuero
- Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Aldo Gaggero
- Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
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25
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Pavia AT. Is Parotitis One More Complication of Influenza? The Ongoing Challenge of Determining Causal Associations. Clin Infect Dis 2018; 67:502-503. [PMID: 29617960 DOI: 10.1093/cid/ciy140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 03/01/2018] [Indexed: 11/13/2022] Open
Affiliation(s)
- Andrew T Pavia
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City
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26
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Boucoiran I, Mayer BT, Krantz EM, Marchant A, Pati S, Boppana S, Wald A, Corey L, Casper C, Schiffer JT, Gantt S. Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants. Pediatr Infect Dis J 2018; 37:627-631. [PMID: 29889809 PMCID: PMC6016842 DOI: 10.1097/inf.0000000000001877] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Most infants with congenital Cytomegalovirus (CMV) infection are born to seropositive women as a result of maternal CMV nonprimary infection (reinfection or reactivation). Although infected children are known to transmit CMV to their seronegative mothers, the frequency and magnitude of nonprimary maternal CMV infection after exposure to viral shedding by children in their household have not been characterized. METHODS A cohort of Ugandan newborns and their mothers were tested weekly for CMV by quantitative polymerase chain reaction of oral swabs. Infant primary infection and maternal nonprimary infection were defined by the onset of persistent high-level oral CMV shedding. Strain-specific antibody testing was used to assess maternal reinfection. Cox regression models with time-dependent covariates were used to evaluate risk factors for nonprimary maternal infection. RESULTS Nonprimary CMV infection occurred in 15 of 30 mothers, all after primary infection of their infants by a median of 6 weeks (range: 1-10) in contrast to none of the mothers of uninfected infants. The median duration of maternal oral shedding lasted 18 weeks (range: 4-42) reaching a median maximum viral load of 4.69 log copies/mL (range: 3.22-5.64). Previous-week infant CMV oral quantities strongly predicted maternal nonprimary infection (hazard ratio: 2.32 per log10 DNA copies/swab increase; 95% confidence interval: 1.63-3.31). Maternal nonprimary infections were not associated with changes in strain-specific antibody responses. CONCLUSIONS Nonprimary CMV infection was common in mothers after primary infection in their infants, consistent with infant-to-mother transmission. Because infants frequently acquire CMV from their mothers, for example, through breast milk, this suggests the possibility of "ping-pong" infections. Additional research is needed to characterize the antigenic and genotypic strains transmitted among children and their mothers.
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Affiliation(s)
- Isabelle Boucoiran
- Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, British Columbia, Canada
| | - Bryan T Mayer
- Fred Hutchinson Cancer Research Center, Seattle, Washington
| | | | - Arnaud Marchant
- Institute for Medical Immunology, Institute for Medical Immunology, Université libre de Bruxelles, Charleroi, Belgium
| | - Sunil Pati
- Department of Pediatrics, University of Alabama Hospital, Birmingham, United Kingdom
| | - Suresh Boppana
- Department of Pediatrics, University of Alabama Hospital, Birmingham, United Kingdom
| | - Anna Wald
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Medicine, University of Washington
| | - Larry Corey
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Medicine, University of Washington
| | - Corey Casper
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Medicine, University of Washington
- Infectious Disease Research Institute, Seattle, Washington
| | - Joshua T Schiffer
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Medicine, University of Washington
| | - Soren Gantt
- Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, British Columbia, Canada
- Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, British Columbia, Canada
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Guidry JT, Birdwell CE, Scott RS. Epstein-Barr virus in the pathogenesis of oral cancers. Oral Dis 2018; 24:497-508. [PMID: 28190296 PMCID: PMC5554094 DOI: 10.1111/odi.12656] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 01/30/2017] [Accepted: 01/31/2017] [Indexed: 12/28/2022]
Abstract
Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that establishes a lifelong persistent infection in the oral cavity and is intermittently shed in the saliva. EBV exhibits a biphasic life cycle, supported by its dual tropism for B lymphocytes and epithelial cells, which allows the virus to be transmitted within oral lymphoid tissues. While infection is often benign, EBV is associated with a number of lymphomas and carcinomas that arise in the oral cavity and at other anatomical sites. Incomplete association of EBV in cancer has questioned if EBV is merely a passenger or a driver of the tumorigenic process. However, the ability of EBV to immortalize B cells and its prevalence in a subset of cancers has implicated EBV as a carcinogenic cofactor in cellular contexts where the viral life cycle is altered. In many cases, EBV likely acts as an agent of tumor progression rather than tumor initiation, conferring malignant phenotypes observed in EBV-positive cancers. Given that the oral cavity serves as the main site of EBV residence and transmission, here we review the prevalence of EBV in oral malignancies and the mechanisms by which EBV acts as an agent of tumor progression.
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Affiliation(s)
- Joseph T. Guidry
- Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, and Feist-Weiller Cancer Center. Louisiana State University Health Sciences Center-Shreveport. Shreveport, LA 71103
| | - Christine E. Birdwell
- Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, and Feist-Weiller Cancer Center. Louisiana State University Health Sciences Center-Shreveport. Shreveport, LA 71103
| | - Rona S. Scott
- Department of Microbiology and Immunology, Center for Tumor and Molecular Virology, and Feist-Weiller Cancer Center. Louisiana State University Health Sciences Center-Shreveport. Shreveport, LA 71103
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Goetsch HE, Zhao L, Gnegy M, Imperiale MJ, Love NG, Wigginton KR. Fate of the Urinary Tract Virus BK Human Polyomavirus in Source-Separated Urine. Appl Environ Microbiol 2018; 84:e02374-17. [PMID: 29374036 PMCID: PMC5861842 DOI: 10.1128/aem.02374-17] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 01/20/2018] [Indexed: 12/11/2022] Open
Abstract
Human polyomaviruses are emerging pathogens that infect a large percentage of the human population and are excreted in urine. Consequently, urine that is collected for fertilizer production often has high concentrations of polyomavirus genes. We studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus (BKPyV) in hydrolyzed source-separated urine with infectivity assays and quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine for long periods of time (T90 [time required for 90% reduction in infectivity or gene copies] of >3 weeks), the viruses were rapidly inactivated (T90 of 1.1 to 11 h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA bacteriophage surrogate T3 (T90 of 24 to 46 days) was much more persistent than that of BKPyV, highlighting a major shortcoming of using bacteriophages as human virus surrogates. Pasteurization and filtration experiments suggest that BKPyV virus inactivation was due to microorganism activity in the source-separated urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is concurrent with inactivation. Our results imply that stored urine does not pose a substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA surrogate do not accurately depict BKPyV fate, and that microbial inactivation is driven by structural elements of the BKPyV capsid.IMPORTANCE We demonstrate that a common urinary tract virus has a high susceptibility to the conditions in hydrolyzed urine and consequently would not be a substantial exposure route to humans using urine-derived fertilizers. The results have significant implications for understanding virus fate. First, by demonstrating that the dsDNA (double-stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity lasting for hours to days, our work highlights the shortcomings of using qPCR to estimate risks from unculturable viruses. Second, commonly used dsDNA surrogate viruses survived for weeks under the same conditions that BK polyomavirus survived for only hours, highlighting issues with using virus surrogates to predict how human viruses will behave in the environment. Finally, our mechanistic inactivation analysis provides strong evidence that microbial activity drives rapid virus inactivation, likely through capsid disassembly. Overall, our work underlines how subtle structural differences between viruses can greatly impact their environmental fate.
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Affiliation(s)
- Heather E Goetsch
- Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Linbo Zhao
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Mariah Gnegy
- Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Michael J Imperiale
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Nancy G Love
- Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Krista R Wigginton
- Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USA
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Prevalence of Human Herpes Viruses in Bronchoalveolar Lavage of Critically Ill Children Undergoing Mechanical Ventilation at a Pediatric Intensive Care Unit. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2018. [DOI: 10.5812/pedinfect.12685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Karalic D, Lazarevic I, Banko A, Cupic M, Jevtovic D, Jovanovic T. Analysis of variability of urinary excreted JC virus strains in patients infected with HIV and healthy donors. J Neurovirol 2017; 24:305-313. [PMID: 29243131 DOI: 10.1007/s13365-017-0608-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 11/10/2017] [Accepted: 11/22/2017] [Indexed: 11/28/2022]
Abstract
In immunocompromised individuals, especially in patients with T cell immunodeficiency, reactivation of JCPyV can cause serious life-threatening diseases. Nowadays, HIV infection is one of the most important factor for reactivation of JCPyV and the development of of the progressive multifocal leukoencephalopathy (PML). Mutations in the outer loops of the VP1 region can lead to the selection of the viral variants with changed tropism and increased pathological potential. The aims of this study were to determine sequence variation and amino acid changes within VP1 loops and the structure of non-coding control region (NCCR) of urinary excreted JCPyV isolates among HIV-infected patients and healthy donors. Single urine samples from 114 HIV-infected patients and 120 healthy donors were collected. PCR was performed for amplification of VP1 and NCCR. Amplified fragments were directly sequenced and analyzed by using bioinformatics tools. Nucleotide substitutions were detected within DE and EF loops and in the β-sheets of both studied groups. In HIV-infected patients group, 70% of mutations were detected within receptor domains. Among healthy donors, one mutation was identified within β-sheets while the remaining were located within receptor domains. The most prevalent mutation was L157V in both groups. Analysis of NCCR revealed that all isolates had archetype structure with some minor changes. Since single point mutations at specific place within outer loop of VP1 region can cause formation of variants with changed receptor specificity, identification of these mutations in HIV-infected patients can help to single out those with higher risk for development of polyomavirus-associated diseases.
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Affiliation(s)
- Danijela Karalic
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia.
| | - Ivana Lazarevic
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia
| | - Ana Banko
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia
| | - Maja Cupic
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia
| | - Djordje Jevtovic
- Clinics of Infectious and Tropical Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia, Bulevar oslobodjenja 16, Belgrade, 11000, Serbia
| | - Tanja Jovanovic
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia, Dr Subotica 1, Belgrade, 11000, Serbia
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31
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Koch RM, Kox M, Thijs EJM, Rahamat-Langendoen JC, van de Veerdonk FL, Gerretsen J, Schloesser J, Diavatopoulos D, Rimmelzwaan GF, Netea MG, van der Hoeven JG, de Jonge MI, Pickkers P. Development of Endotoxin Tolerance Does Not Influence the Response to a Challenge with the Mucosal Live-Attenuated Influenza Vaccine in Humans In Vivo. Front Immunol 2017; 8:1600. [PMID: 29312282 PMCID: PMC5732479 DOI: 10.3389/fimmu.2017.01600] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 11/06/2017] [Indexed: 01/11/2023] Open
Abstract
Introduction The effects of bacterial infections on the response to subsequent viral infections are largely unknown. This is important to elucidate to increase insight into the pathophysiology of bacterial and viral co-infections, and to assess whether bacterial infections may influence the course of viral infections. Methods Healthy male subjects received either bacterial endotoxin [Escherichia coli-derived lipopolysaccharide (LPS), 2 ng/kg, n = 15] or placebo (n = 15) intravenously, followed by intranasal Fluenz (live-attenuated influenza vaccine) 1 week later. Results LPS administration resulted in increased plasma cytokine levels and development of endotoxin tolerance in vivo and ex vivo, illustrated by attenuated cytokine production upon rechallenge with LPS. Following Fluenz administration, infectivity for the Fluenz A/B strains was similar between the LPS-Fluenz and placebo-Fluenz groups (13/15 subjects in both groups). Also, the Fluenz-induced increase in temperature and IL-6, G-CSF and IP-10 concentrations in nasal wash were similar between both groups. Conclusion While endotoxemia profoundly attenuates the immune response upon a second LPS challenge, it does not influence the Fluenz-induced immune response. These results suggest immune suppression after bacterial infection does not alter the response to a subsequent viral infection.
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Affiliation(s)
- Rebecca M Koch
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.,Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands
| | - Matthijs Kox
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.,Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands
| | - Eleonora J M Thijs
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Janette C Rahamat-Langendoen
- Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Frank L van de Veerdonk
- Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands.,Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Jelle Gerretsen
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.,Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands
| | | | - Dimitri Diavatopoulos
- Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Guus F Rimmelzwaan
- Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands
| | - Mihai G Netea
- Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands.,Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Johannes G van der Hoeven
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.,Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands
| | - Marien I de Jonge
- Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands.,Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.,Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands
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Ma FL, Li DD, Wei TL, Li JS, Zheng LS. Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real-time TaqMan-based PCR. Virol J 2017; 14:152. [PMID: 28806976 PMCID: PMC5557062 DOI: 10.1186/s12985-017-0817-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 08/01/2017] [Indexed: 01/02/2023] Open
Abstract
Background Human Malawi polyomavirus (MWPyV) was discovered in 2012, but its prevalence and clinical characteristics are largely unknown. Methods We used real-time TaqMan-based PCR to detect MWPyV in the feces (n = 174) of children with diarrhea, nasopharyngeal aspirates (n = 887) from children with respiratory infections, and sera (n = 200) from healthy adults, and analyzed its clinical characteristics statistically. All the MWPyV-positive specimens were also screened for other common respiratory viruses. Results Sixteen specimens were positive for MWPyV, including 13 (1.47%) respiratory samples and three (1.7%) fecal samples. The samples were all co-infected with other respiratory viruses, most commonly with influenza viruses (69.2%) and human coronaviruses (30.7%). The MWPyV-positive children were diagnosed with bronchopneumonia or viral diarrhea. They ranged in age from 12 days to 9 years, and the most frequent symptoms were cough and fever. Conclusions Real-time PCR is an effective tool for the detection of MWPyV in different types of samples. MWPyV infection mainly occurs in young children, and fecal–oral transmission is a possible route of its transmission. Electronic supplementary material The online version of this article (doi:10.1186/s12985-017-0817-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fen-Lian Ma
- Key Laboratory for Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing, 100052, China
| | - Dan-di Li
- Key Laboratory for Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing, 100052, China
| | - Tian-Li Wei
- Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100052, China
| | - Jin-Song Li
- Key Laboratory for Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing, 100052, China
| | - Li-Shu Zheng
- Key Laboratory for Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, 100 Ying-Xin St., Xi-Cheng District, Beijing, 100052, China.
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Epstein-Barr virus: a master epigenetic manipulator. Curr Opin Virol 2017; 26:74-80. [PMID: 28780440 DOI: 10.1016/j.coviro.2017.07.017] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 07/10/2017] [Accepted: 07/18/2017] [Indexed: 12/29/2022]
Abstract
Like all herpesviruses, the ability of Epstein-Barr virus (EBV) to establish life-long persistent infections is related to a biphasic viral lifecycle that involves latency and reactivation/lytic replication. Memory B cells serve as the EBV latency compartment where silencing of viral gene expression allows maintenance of the viral genome, avoidance of immune surveillance, and life-long carriage. Upon viral reactivation, viral gene expression is induced for replication, progeny virion production, and viral spread. EBV uses the host epigenetic machinery to regulate its distinct viral gene expression states. However, epigenetic manipulation by EBV affects the host epigenome by reprogramming cells in ways that leave long-lasting, oncogenic phenotypes. Such virally-induced epigenetic alterations are evident in EBV-associated cancers.
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Osman M, Al Salihi M, Abu Sitta E, Al Hadidi S. A rare case of Epstein-Barr virus mucocutaneous ulcer of the colon. BMJ Case Rep 2017; 2017:bcr-2017-220717. [PMID: 28687701 PMCID: PMC5535207 DOI: 10.1136/bcr-2017-220717] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/16/2017] [Indexed: 11/04/2022] Open
Abstract
Epstein-Barr virus mucocutaneous ulcer (EBVMCU) is a rare form of EBV lymphoproliferative disorder. The disease was recently described in 2010 for the first time in a case series and it was recently identified by the WHO classification of haematological malignancies as a separate category among the EBV lymphoproliferative disorders. We present a case of EBVMCU of the colon presenting as an ulcerating inflammatory mass in a female in her mid-60s who presented initially with abdominal pain and diarrhoea. The patient had extensive workup for her disease and due to progression of her symptoms, she was taken for an exploratory laparotomy. During the procedure, there was an inflammatory mass at the caecum and severe inflammation of the caecum and the terminal ileum and right hemicolectomy was performed. Diagnosis was confirmed by histopathology as EBV-positive lymphoproliferative disorder best classified as EBV-positive mucocutaneous ulcer.
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Affiliation(s)
- Mohammed Osman
- Department of Internal Medicine, Hurley Medical Center, Flint, Michigan, USA
| | - Mohammed Al Salihi
- Department of Internal Medicine, Hurley Medical Center, Flint, Michigan, USA
| | - Emad Abu Sitta
- Department of Internal Medicine, Hurley Medical Center, Flint, Michigan, USA
| | - Samer Al Hadidi
- Department of Internal Medicine, Hurley Medical Center /Michigan State University, Flint, Michigan, USA
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Hussain I, Tasneem F, Umer M, Pervaiz A, Raza M, Arshad MI, Shahzad N. Specific and quantitative detection of Human polyomaviruses BKPyV and JCPyV in the healthy Pakistani population. Virol J 2017; 14:86. [PMID: 28438210 PMCID: PMC5404684 DOI: 10.1186/s12985-017-0752-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 04/19/2017] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The BK Polyomavirus (BKPyV) and JC polyomavirus (JCPyV) infections are widespread in human population and have been associated with severe kidney and brain disorders, respectively. The viruses remain latent primarily in reno-urinary tract, reactivating only in case of a compromised immune system. The seroepidemiology and molecular prevalence of BKPyV and JCPyV have been widely studied both in healthy and immunocompromised patients worldwide. However, data regarding the prevalence of these viruses in the immunocompetent or apparently healthy Pakistani population is lacking. Herein, we present the first ever report on quantitative prevalence of BKPyV and JCPyV in the peripheral blood of a randomly selected cohort of healthy Pakistani population. METHODS A total of 266 whole blood samples were examined. The subjects were divided into three age groups: ≤ 25 years (young), 26-50 years (middle) and ≥ 51 years (elder). Absolute real time PCR assay was designed to quantify the BKPyV and JCPyV viral copy numbers in the range of 106 to 100 copies/mL. RESULTS Overall, BKPyV was detected in 27.1% (72/266) individuals while JCPyV in 11.6% (31/266) indicating significant difference (p < 0.005) in the distribution of these two viruses. The prevalence of BKPyV significantly decreased from 51% (49/96) in young age group to 8.2% (7/85) in eldest age group. Whereas, JCPyV positivity rate slightly increased from 8.3% (8/96) in young age group to 11.8% (10/85) in elder age group. The median viral load was calculated as 6.2 log and 3.38 log copies/mL of blood for BKPyV and JCPyV, respectively. Notably, no significant difference in viral load of either of the subtypes was found between different age groups. CONCLUSION The current study provides an important baseline data on the prevalence and viral load of circulating BKPyV and JCPyV in Pakistani population. The prevalence and viral load of BKPyV was comparatively higher than JCPyV. The prevalence of BKPyV significantly decreased with increase in age while JCPyV positivity rate slightly increased with increasing age. Viral load of both BKPyV and JCPyV was not correlated with the individual ages.
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Affiliation(s)
- Iqra Hussain
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan
| | - Fareeda Tasneem
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Muhammed Umer
- National Institute for Biotechnology & Genetic Engineering, Faisalabad, Pakistan
| | - Ayesha Pervaiz
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan
| | - Muslim Raza
- Department of Mathematics and Statistics, Virtual University of Pakistan, Lahore, Pakistan
| | | | - Naveed Shahzad
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
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From Evolutionary Advantage to Disease Agents: Forensic Reevaluation of Host-Microbe Interactions and Pathogenicity. Microbiol Spectr 2017; 5. [PMID: 28155809 DOI: 10.1128/microbiolspec.emf-0009-2016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
As the "human microbiome era" continues, there is an increasing awareness of our resident microbiota and its indispensable role in our fitness as holobionts. However, the host-microbe relationship is not so clearly defined for some human symbionts. Here we discuss examples of "accidental pathogens," meaning previously nonpathogenic and/or environmental microbes thought to have inadvertently experienced an evolutionary shift toward pathogenicity. For instance, symbionts such as Helicobacter pylori and JC polyomavirus have been shown to have accompanied humans since prehistoric times and are still abundant in extant populations as part of the microbiome. And yet, the relationship between a subgroup of these microbes and their human hosts seems to have changed with time, and they have recently gained notoriety as gastrointestinal and neuropathogens, respectively. On the other hand, environmental microbes such as Legionella spp. have recently experienced a shift in host range and are now a major problem in industrialized countries as a result of artificial ecosystems. Other variables involved in this accidental phenomenon could be the apparent change or reduction in the diversity of human-associated microbiota because of modern medicine and lifestyles. All of this could result in an increased prevalence of accidental pathogens in the form of emerging pathogens.
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Polyomaviruses. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00168-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Chanouzas D, Dyall L, Nightingale P, Ferro C, Moss P, Morgan MD, Harper L. Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial. Trials 2016; 17:338. [PMID: 27450392 PMCID: PMC4957324 DOI: 10.1186/s13063-016-1482-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 06/17/2016] [Indexed: 12/31/2022] Open
Abstract
Background The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality. Considerable evidence suggests that CD4 + CD28null T-cell expansions, predominantly seen in Cytomegalovirus (CMV) seropositive individuals, are associated with systemic dysregulation of immune function leading to a heightened risk of infection and cardiovascular disease. In patients with AAV, CD4 + CD28null expansions are driven by CMV and are associated with an increased risk of infection and mortality. The aim of this study is to explore in detail the ways in which CMV modulates the immune system and to determine whether treatment with valaciclovir blocks subclinical CMV reactivation in CMV seropositive AAV patients and ameliorates the CMV-induced adverse effects on the immune system. Methods/design CANVAS is a single-centre prospective open-label randomised controlled proof-of-concept trial of 50 adult CMV seropositive patients with stable AAV. Participants will be randomly allocated to receive valaciclovir orally (2 g QDS or reduced according to renal function) or no additional treatment for 6 months with an additional 6-month follow-up period. The primary outcome is the proportion of patients with CMV reactivation, as assessed by measurable viral load on quantitative blood and urine CMV polymerase chain reaction. The secondary outcomes are safety, change in the proportion of CD4+ CMV-specific T-cell population (defined as CD4 + CD28null cells) and change in soluble markers of inflammation from baseline to 6 months. Further tertiary and exploratory outcomes include persistence of the effect of valaciclovir on the proportion of CD4 + CD28null cells at 6 months post completion of treatment, change in the immune phenotype of CD4+ T cells and change in blood pressure and arterial stiffness parameters from baseline to 6 months. Discussion The results of this study will enable larger studies to be conducted to determine whether by controlling subclinical CMV reactivation, we can improve clinical endpoints such as infection and cardiovascular disease. The potential impact of this study is not limited to AAV, as CD4 + CD28null cells have been linked to adverse outcomes in other inflammatory conditions and in the context of an ageing immune system. Trial registration ClinicalTrials.gov Identifier NCT01633476 (registered 29 June 2012). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1482-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Dimitrios Chanouzas
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Lovesh Dyall
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Peter Nightingale
- Wolfson Computer Laboratory, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Charles Ferro
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Paul Moss
- School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Matthew David Morgan
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Lorraine Harper
- School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia. Microb Pathog 2016; 97:204-8. [PMID: 27317859 DOI: 10.1016/j.micpath.2016.06.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 06/10/2016] [Accepted: 06/14/2016] [Indexed: 12/14/2022]
Abstract
The human polyomaviruses BKPyV and JCPyV are members of Polyomaviridae family and after primary infections they persist as latent infection especially in the kidneys. BKVPy reactivation is mainly related to a renal nephropathy and JCV reactivation can induce the progressive multifocal leukoencephalopathy. The aim of this study was to investigate and to compare the presence of BKPyV and JCPyV in urine and plasma samples from immunocompromised and immunocompetent groups. The viral detection and quantification was done by a real time PCR from 100 healthy individuals and from 72 kidney transplanted patients (KTx) enrolled in a prospective study. Polyomavirus DNA urinary shedding was identified in 19% of healthy person, BKPyV in 6%; JCPyV more frequent in 13%. No individuals in this group developed polyomavirus viremia. BKPyV and JCPyV viruria was seen in 36% and 28% of KTx respectively, and 11% had a concomitant BKPyV and JCPyV viruria. Only BKPy viremia was detected in 5.5% of the KTx. In healthy persons, JCPyV shedding was associated with older individuals. However, in KTx, BKPyV was associated with younger age and male gender. No significant association was found between the patient's origin and BKPyV or JCPyV infection. In conclusion and consisting with previous reports, BKPyV and JCPyV prevalence and urinary loads were significantly higher in immunosuppressed compared to non-immunosuppressed individuals. In Addition and by contrast to KTx, JCPyV was more frequent than BKPyV in healthy individuals. Furthermore, the shedding of both polyomaviruses was differently associated with the age and the sex according to each population.
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Papa N, Zanotta N, Knowles A, Orzan E, Comar M. Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection. Virol J 2016; 13:97. [PMID: 27287743 PMCID: PMC4901423 DOI: 10.1186/s12985-016-0553-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 06/01/2016] [Indexed: 01/22/2023] Open
Abstract
Background The novel Malawi polyomavirus (MWPyV) was initially detected in stool specimens from healthy children and children with gastrointestinal symptoms, mostly diarrhea, indicating that MWPyV might play a role in human gastroenteric diseases. Recently, MWPyV sequences were additionally identified in respiratory secretions from both healthy and acutely ill children suggesting that MWPyV may have a tropism for different human tissues. This study was designed to investigate the possible sites of latency/persistence for MWPyV in a cohort of healthy Italian children. Methods Specimens (n° 500) of tonsils, adenoids, blood, urines and feces, from 200 healthy and immunocompetent children (age range: 1–15 years) were tested for the amplification of the MWPyV LT antigen sequence by quantitative real-time PCR. Samples (n° 80) of blood and urines from 40 age-matched children with autoimmune diseases, were screened for comparison. Polyomaviruses JC/BK and Epstein-Barr Virus (EBV) were also tested as markers of infection in all samples using the same molecular technique. Results In our series of healthy children, MWPyV was detected only in the lymphoid tissues showing a prevalence of 6 % in tonsils and 1 % in adenoids, although with a low viral load. No JCPyV or BKPyV co-infection was found in MWPyV positive samples, while EBV showed a similar percentage of both in tonsils and adenoids (38 and 37 %). Conversely, no MWPyV DNA was detected in stool from babies with gastroenteric syndrome. With regards to autoimmune children, neither MWPyV nor BKPyV were detected in blood, while JCPyV viremia was observed in 15 % (6/40) of children treated with Infliximab. Urinary BKPyV shedding was observed in 12.5 % (5/40) while JCPyV in 100 % of the samples. Conclusions The detection of MWPyV sequences in tonsils and adenoids of healthy children suggests that secondary lymphoid tissues can harbour MWPyV probably as transient sites of persistence rather than actual sites of latency.
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Affiliation(s)
- N Papa
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65, 34137, Trieste, Italy
| | - N Zanotta
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65, 34137, Trieste, Italy
| | - A Knowles
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65, 34137, Trieste, Italy
| | - E Orzan
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65, 34137, Trieste, Italy
| | - M Comar
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65, 34137, Trieste, Italy. .,Medical Sciences Department, University of Trieste, Piazzale Europa 1, 34128, Trieste, Italy.
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Epstein-Barr virus dynamics in asymptomatic immunocompetent adults: an intensive 6-month study. Clin Transl Immunology 2016; 5:e81. [PMID: 27350880 PMCID: PMC4910122 DOI: 10.1038/cti.2016.28] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 04/14/2016] [Accepted: 04/15/2016] [Indexed: 11/09/2022] Open
Abstract
Characterizing Epstein-Barr virus (EBV) dynamics in asymptomatic immunocompetent persons provides a baseline for defining quantitative thresholds associated with EBV disease. Studying latent membrane protein (LMP)-1 sequence variation over time could establish the rates of reactivation and superinfection, and also trace transmission. Twelve asymptomatic adult subjects were evaluated prospectively nine times over 6 months. EBV serum antibodies were measured by enzyme immunoassay. EBV DNA in oral and whole-blood samples was quantitated by real-time (TaqMan) PCR and analyzed for LMP-1 sequence variability. All 11 antibody positive subjects had EBV DNA detected in their oral compartment at least once during the 6-month study. The quantities ranged from 1.70 to 4.91 log10 copies EBV per ml of oral cell pellet. One subject was continuously viremic for 79 days. Overall, EBV DNA was detected in 63 (24%) of 260 samples from 11 antibody-positive subjects and in 0/27 samples from an antibody-negative subject. The quantities in positive samples ranged from 1.7 to 4.9 log10 copies EBV per ml. EBV LMP-1 gene sequence variations in subjects were constant over time regardless of the compartment sampled. Subjects 18-30 years old had EBV DNA detected more frequently than subjects >30 years old (38/108 positive samples versus 25/152; P<0.001). In conclusion, EBV DNA shedding is common in asymptomatic adults. The younger adults shed more frequently, which may reflect a shorter time from their primary EBV infection to sampling. The LMP-1 sequence analysis method employed here could be used to trace person-to-person transmission because patterns remained almost identical over time.
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Domínguez-Mozo MI, Toledano-Martínez E, Rodríguez-Rodríguez L, García-Montojo M, Alvarez-Lafuente R, Fernández-Gutiérrez B. JC virus reactivation in patients with autoimmune rheumatic diseases treated with rituximab. Scand J Rheumatol 2016; 45:507-511. [DOI: 10.3109/03009742.2015.1135980] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- MI Domínguez-Mozo
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
| | - E Toledano-Martínez
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
| | - L Rodríguez-Rodríguez
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
| | - M García-Montojo
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
| | - R Alvarez-Lafuente
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
| | - B Fernández-Gutiérrez
- Departments of Neurology and Rheumatology, Health Research Institute, San Carlos Clinical Hospital (IDISSC), Madrid, Spain
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Umbro I, Tinti F, Muiesan P, Mitterhofer AP. Different behaviour of BK-virus infection in liver transplant recipients. World J Gastroenterol 2016; 22:1532-1540. [PMID: 26819520 PMCID: PMC4721986 DOI: 10.3748/wjg.v22.i4.1532] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 10/10/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.
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The impact of donor viral replication at transplant on recipient infections posttransplant: a prospective study. Transplantation 2015; 99:602-8. [PMID: 25148381 DOI: 10.1097/tp.0000000000000354] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Organ donors are often implicated as the source of posttransplant recipient infection. We prospectively studied kidney and liver donor-recipient pairs to determine if donor viral replication of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) at transplant was a risk factor for posttransplant recipient infection and disease. METHODS Donors and recipients were studied for antibodies against CMV and EBV and for quantitative viral replication of CMV, EBV, and BKV in oral washes, urine, and whole blood pretransplant. Recipient testing continued every 3 months after transplantation. Demographic and clinical data on infections and graft and subject outcomes were obtained. RESULTS The 98 donor-recipient pairs included 15 liver and 83 kidney transplants (18 of whom were children). No donor had detectable CMV replication; therefore, its impact on recipient CMV replication could not be analyzed. Donor EBV replication occurred in 22%, mostly in the oral wash and showed no impact on posttransplant recipient EBV replication (P=0.9) or EBV viremia (P=0.6) in kidney or liver recipients. Donor BKV replication occurred in 17%, mostly in the urine and although not associated with posttransplant recipient urinary BKV replication in recipients, it was associated with BKV viremia (P=0.02), and a significantly shorter time to BKV viremia (P=0.01) in kidney recipients. CONCLUSION Donor replication of CMV or EBV did not impact posttransplant recipient viral replication in kidney or liver transplants. Donor urinary BKV replication is associated with recipient BKV viremia in kidney transplants.
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Moran NR, Webster B, Lee KM, Trotman J, Kwan YL, Napoli J, Leong RW. Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn’s disease. World J Gastroenterol 2015; 21:6072-6076. [PMID: 26019475 PMCID: PMC4438045 DOI: 10.3748/wjg.v21.i19.6072] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn’s disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn’s disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease.
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Shaheli M, Yaghobi R, Rezaeian A, Iravani Saadi M, Ramzi M. Study of the Associations Between TT Virus Single and Mixed Infections With Leukemia. Jundishapur J Microbiol 2015; 8:e18212. [PMID: 26034552 PMCID: PMC4449851 DOI: 10.5812/jjm.8(4)2015.18212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 10/23/2014] [Accepted: 11/02/2014] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND The pathogenic association of Transfusion Transmitted Virus or Torque teno Virus (TT Virus) single and mixed infections with leukemia was under evaluation in these years but confront with controversies. This hypothesis is based on the higher prevalence of TT Virus infection in patients with leukemia compared with controls. OBJECTIVES The aim of this study was to determine the frequency of TT Virus, Cytomegalovirus (CMV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections in patients with leukemia and healthy controls. PATIENTS AND METHODS In this cross sectional study, 95 patients with leukemia and 100 healthy controls who were admitted to the Namazi Hospital affiliated to the Shiraz University of Medical Sciences, Shiraz, Iran, were enrolled between years 2012 and 2013. Blood samples treated with EDTA were collected from each patient with leukemia and controls. The existence of TT Virus infection was analyzed using the semi-nested PCR method. The immunological prevalence of HBV and HCV infections were evaluated using HBs-Ag and HCV-Ab ELISA based protocols, respectively. Active CMV infection was also evaluated using an immunofluorescence method. Also risk factors of leukemia and viral infections were statistically analyzed in patients with leukemia. RESULTS The TT Virus infection was significantly found in 40 of 95 (42.1%) and 12 of 100 (12%) patients with leukemia and controls, respectively. The HBs-Ag and HCV-Ab were detected in 27 of 95 (28.4%) and 18 of 69 (26.1%) patients with leukemia but were not found in the controls. Active CMV infection was also found in 11 of 69 (16%) patients and none of the controls. Significant co-infection of TT Virus was found with HBV (15 of 40; 37.5%), HCV (14 of 40; 35%) and CMV (7 of 40; 17.5%) in patients with leukemia. CONCLUSIONS Confirmation of the significantly higher frequency of TT Virus, HBV, HCV and CMV single infection and their co-infection in patients with leukemia compared with healthy controls, emphasizes the determinative role of TT Virus pathogenesis in clinical outcomes observed in patients with leukemia, which requires extensive evaluation by further studies.
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Affiliation(s)
- Marjan Shaheli
- Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, IR Iran
| | - Ramin Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding author: Ramin Yaghobi, Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel: +98-7116476331, Fax: +98-7116476331, E-mail:
| | - Abbasali Rezaeian
- Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, IR Iran
| | | | - Mani Ramzi
- Hematology Research Center and Bone Marrow Transplant Unit, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Abstract
Infections caused by viruses are universal during childhood and adolescence. Clinicians will regularly care for children and adolescents who present with infections caused by a wide number of viral pathogens. These infections have varied presentations. Many infections may have clinical presentations that are specific to the infecting virus but present differently, based on the age and immunocompetence of the patient. Some children are directly impacted early in their lives when maternal disease results in an in utero infection (cytomegalovirus, rubella virus, or parvovirus B19). Other viruses may infect children in a predictable pattern as they grow older (rhinovirus or influenza virus). Fortunately, many viral infections frequently encountered in the past are no longer extant due to widespread immunization efforts. Recognition of these vaccine-preventable infections is important because outbreaks of some of these diseases (mumps or measles) continue to occur in the United States. Vigilance in vaccine programs against these viral agents can prevent their re-emergence. In addition, an increasing number of viral infections (herpes simplex virus, influenza virus, varicella zoster virus, or cytomegalovirus) can now be successfully treated with antiviral medications. Most viral infections in children result in self-limited illness and are treated symptomatically and infected children experience full recovery. This review will address the epidemiology, clinical presentation, diagnosis, treatment, and prevention of viral infections commonly encountered by the clinician.
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Kuhara T, Watanabe D, Ishida N, Tamada Y, Matsumoto Y, Ihira M, Fukaya S, Yoshida S, Yoshikawa T, Asano Y. Quantitative analysis of shedding of Epstein-Barr virus in saliva from patients with connective tissue diseases: a pilot study. Int J Dermatol 2015; 52:887-90. [PMID: 23789606 DOI: 10.1111/j.1365-4632.2011.04992.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Lednicky JA, Butel JS, Luetke MC, Loeb JC. Complete genomic sequence of a new Human polyomavirus 9 strain with an altered noncoding control region. Virus Genes 2014; 49:490-2. [PMID: 25260554 DOI: 10.1007/s11262-014-1119-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 09/20/2014] [Indexed: 12/21/2022]
Abstract
A complete Human polyomavirus 9 (HPyV9) genome, designated HPyV9 UF-1, was amplified by rolling circle DNA amplification from DNA extracted from the peripheral blood mononuclear cells (PBMC) of an AIDS patient. The noncoding control (enhancer/promoter) region (NCCR) of HPyV9 UF-1 has one less AML-1a binding site and three more potential Sp1/GC box binding sites than the NCCRs of two previously described HPyV9 genomes. Nucleotide polymorphisms within the coding regions result in two amino acid differences in the deduced VP2 and VP3 proteins of HPyV9 UF-1 relative to those of the two previously described HPyV9 genomes. Exhaustive attempts to detect HPyV9 in DNA samples extracted from the PBMC of 40 healthy humans and 9 other AIDS patients were unsuccessful, highlighting the need for improved search strategies and optimal specimens for the detection of HPyV9 in humans.
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Affiliation(s)
- John A Lednicky
- Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Box 100188, Gainesville, FL, 32610-0188, USA,
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Carruthers RL, Berger J. Progressive multifocal leukoencephalopathy and JC Virus-related disease in modern neurology practice. Mult Scler Relat Disord 2014; 3:419-30. [DOI: 10.1016/j.msard.2014.01.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Revised: 01/30/2014] [Accepted: 01/31/2014] [Indexed: 11/25/2022]
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