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Tang J, Chen S, Deng Y, Liu J, Huang D, Fu M, Xue B, Liu C, Wu C, Wang F, Zhou Y, Yang Q, Chen X. MA104 cell line is permissive for human bocavirus 1 infection. J Virol 2025; 99:e0153924. [PMID: 39846742 PMCID: PMC11852709 DOI: 10.1128/jvi.01539-24] [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: 09/14/2024] [Accepted: 12/13/2024] [Indexed: 01/24/2025] Open
Abstract
Human bocavirus 1 (HBoV1) has appeared as an emerging pathogen, causing mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children and immunocompromised individuals. The lack of cell lines suitable for culturing replicative viruses hinders research on HBoV1. Here, we characterized the susceptibility to HBoV1 of 29 human and 7 animal cell lines, and identified a permissive cell line, MA104. The complete HBoV1 life cycle was achieved in MA104 cells, including viral entry, complete replication, and infectious progeny virion production. Additionally, the suppression of the interferon pathway facilitated the viral genome replication in MA104 cells. RNA-sequencing showed that innate immunity, inflammation, the PI3K-Akt and MAPK signaling pathways, and the cellular membrane system were mobilized in response to HBoV1 infection. Overall, our study is the first to identify a cell line, MA104, that supports the complete HBoV1 life cycle, which will promote research on HBoV1 virology and pathogenesis and benefit drug and vaccine development.IMPORTANCEHBoV1 is an emerging pathogen that mainly causes respiratory tract infections, while the lack of cell lines suitable for culture replicative viruses hindered research on HBoV1. Here, we identify a permissive cell line for HBoV1 infection, MA104, and reveal that the complete life cycle of HBoV1 was supported in MA104 cells. Our findings provide a suitable cell model for the study of HBoV1 and explore its application for antiviral drug evaluation, which is vital for research on HBoV1 virology and pathogenesis, as well as for drug and vaccine development.
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Affiliation(s)
- Jielin Tang
- Guangzhou National Laboratory, Guangzhou, China
- Guangzhou Medical University, Guangzhou, China
| | - Sijie Chen
- GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China
| | - Yijun Deng
- Guangzhou National Laboratory, Guangzhou, China
- Guangzhou Medical University, Guangzhou, China
| | - Junjun Liu
- Guangzhou National Laboratory, Guangzhou, China
| | - Dan Huang
- Guangzhou National Laboratory, Guangzhou, China
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
| | - Muqing Fu
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Bao Xue
- Guangzhou National Laboratory, Guangzhou, China
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
| | - Canyu Liu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
| | - Chunchen Wu
- Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fan Wang
- GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China
| | - Yuan Zhou
- Guangzhou National Laboratory, Guangzhou, China
| | - Qi Yang
- Guangzhou National Laboratory, Guangzhou, China
- Guangzhou Medical University, Guangzhou, China
| | - Xinwen Chen
- Guangzhou National Laboratory, Guangzhou, China
- Guangzhou Medical University, Guangzhou, China
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
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Trapani S, Caporizzi A, Ricci S, Indolfi G. Human Bocavirus in Childhood: A True Respiratory Pathogen or a "Passenger" Virus? A Comprehensive Review. Microorganisms 2023; 11:1243. [PMID: 37317217 DOI: 10.3390/microorganisms11051243] [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] [Received: 03/31/2023] [Revised: 05/04/2023] [Accepted: 05/08/2023] [Indexed: 06/16/2023] Open
Abstract
Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and lower respiratory tract infections in adults and children. However, its role as a respiratory pathogen is still not fully understood. It has been reported both as a co-infectious agent (predominantly with respiratory syncytial virus, rhinovirus, parainfluenza viruses, and adenovirus), and as an isolated viral pathogen during respiratory tract infections. It has also been found in asymptomatic subjects. The authors review the available literature on the epidemiology of HBoV, the underlying risk factors associated with infection, the virus's transmission, and its pathogenicity as a single pathogen and in co-infections, as well as the current hypothesis about the host's immune response. An update on different HBoV detection methods is provided, including the use of quantitative single or multiplex molecular methods (screening panels) on nasopharyngeal swabs or respiratory secretions, tissue biopsies, serum tests, and metagenomic next-generations sequencing in serum and respiratory secretions. The clinical features of infection, mainly regarding the respiratory tract but also, though rarely, the gastrointestinal one, are extensively described. Furthermore, a specific focus is dedicated to severe HBoV infections requiring hospitalization, oxygen therapy, and/or intensive care in the pediatric age; rare fatal cases have also been reported. Data on tissue viral persistence, reactivation, and reinfection are evaluated. A comparison of the clinical characteristics of single infection and viral or bacterial co-infections with high or low HBoV rates is carried out to establish the real burden of HBoV disease in the pediatric population.
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Affiliation(s)
- Sandra Trapani
- Department of Health Sciences, University of Florence, Viale Pieraccini, 24, 50139 Florence, Italy
- Pediatric Unit, Meyer Children's Hospital IRCCS, Viale Pieraccini, 24, 50139 Florence, Italy
| | - Alice Caporizzi
- Pediatric Unit, Meyer Children's Hospital IRCCS, Viale Pieraccini, 24, 50139 Florence, Italy
| | - Silvia Ricci
- Department of Health Sciences, University of Florence, Viale Pieraccini, 24, 50139 Florence, Italy
- Division of Immunology, Meyer Children's Hospital IRCCS, Viale Pieraccini, 24, 50139 Florence, Italy
| | - Giuseppe Indolfi
- Pediatric Unit, Meyer Children's Hospital IRCCS, Viale Pieraccini, 24, 50139 Florence, Italy
- NEUROFARBA Department, University of Florence, Viale Pieraccini, 24, 50139 Florence, Italy
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Ji K, Sun J, Yan Y, Han L, Guo J, Ma A, Hao X, Li F, Sun Y. Epidemiologic and clinical characteristics of human bocavirus infection in infants and young children suffering with community acquired pneumonia in Ningxia, China. Virol J 2021; 18:212. [PMID: 34715898 PMCID: PMC8554736 DOI: 10.1186/s12985-021-01682-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 10/18/2021] [Indexed: 01/13/2023] Open
Abstract
Background Pneumonia has a high incidence rate and is a major cause of mortality in children, mostly community-acquired pneumonia (CAP). Human bocavirus (HBoV), since it first identified in 2005, has been repeatedly associated with respiratory tract infections. Nevertheless, the role and related information of HBoV as a pathogen of CAP has not been fulfilled. Here our study is to assess the epidemiological and clinical features in HBoV-positive children with CAP. Methods A total of 878 secretions of lower respiratory samples were obtained, multiplex PCR was used to detect HBoV and other respiratory viruses. Results Of all cases, HBoV was detected in 10.0%, with a peak incidence of infection among children < 2 year old, and predominantly noted in autumn and winter. Only 8 patients were HBoV single infection. Co-infection with other respiratory viruses was observed in 86.4%. Moreover, co-infection with bacteria occurred in 27.3% and with Mycoplasma pneumoniae (MP) in 33.0% of HBoV-positive patients. Among all HBoV-positive samples co-infected with bacteria, 87.5% are gram negative bacteria. Compared with HBoV-negative group, age (P = 0.048), wheezing (P = 0.015), tachypnea (P = 0.016), lactate dehydrogenase (P = 0.026) and severe pneumonia (P = 0.023) were statistically significant in HBoV-positive patients. Furthermore, HBoV-positive patients less than 1 year old were more likely to have co-infection with bacteria (P = 0.007). Conclusions HBoV can be detected alone in respiratory samples of children with CAP, maybe it is one of the causes of CAP in infants. The high incidence of severe pneumonia was found in HBoV-positive patients compared with HBoV-negative cases may indicate a relationship between severe pneumonia and HBoV.
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Affiliation(s)
- Kai Ji
- Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Science, Ningxia Medical University, Yinchuan, 750004, China
| | - Jinhan Sun
- School of Clinical Medicine, Hainan Medical University, Haikou, 571199, China
| | - Yan Yan
- Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Science, Ningxia Medical University, Yinchuan, 750004, China
| | - Lei Han
- Department of Clinical Laboratory, Yinchuan Women and Children Healthcare Hospital, Yinchuan, 750001, China
| | - Jianhui Guo
- Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Science, Ningxia Medical University, Yinchuan, 750004, China
| | - Anwen Ma
- Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Science, Ningxia Medical University, Yinchuan, 750004, China
| | - Xueqi Hao
- Department of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, China
| | - Fang Li
- Department of Respiratory and Critical Care, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
| | - Yuning Sun
- Department of Biochemistry and Molecular Biology, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Science, Ningxia Medical University, Yinchuan, 750004, China.
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Polo D, Lema A, Gándara E, Romalde JL. Prevalence of human bocavirus infections in Europe. A systematic review and meta-analysis. Transbound Emerg Dis 2021; 69:2451-2461. [PMID: 34250765 DOI: 10.1111/tbed.14233] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/18/2021] [Accepted: 07/09/2021] [Indexed: 11/29/2022]
Abstract
Human bocaviruses (HBoVs) are recently described as human emergent viruses, especially in young children. In this study, we undertook a systematic review and meta-analysis to estimate their prevalence in Europe. PubMed, Web of Science and Scopus databases were systematically screened for clinical studies, up to October 2020. Study eligibility criteria were primary full-text articles from clinical studies, conducted using valid screening test methods and published in peer-reviewed journals, in English or Spanish and from European countries. The overall pooled prevalence, prevalence by country as well as the prevalence of HBoV as a single or co-pathogen were estimated using a random-effects model. Sub-group and meta-regression analyses explored potential sources of heterogeneity in the data. A total of 35 studies involving 32,656 subjects from 16 European countries met the inclusion criteria. Heterogeneity (I2 = 97.0%, p < .01) was seen among studies; HBoV prevalence varied from 2.0 to 45.69% with a pooled estimate of 9.57% (95%CI 7.66-11.91%). The HBoV prevalence both as a single infection (3.99%; 95%CI 2.99-5.31%) or as co-infection with other viruses (5.06%; 95%CI 3.88-6.58%) was also analysed. On a geographic level, prevalence by country did not show statistical differences, ranging from 3.24% (Greece) to 21.05% (Denmark). An odds ratio analysis was also included in order to evaluate the relevance of the variable 'age' as a risk factor of HBoV infection in children <5 years old. The OR value of 1.77 (95%CI 1.13-2.77; p < .01) indicated that being <5 years old is a risk factor for HBoV infection. This study showed that HBoV has a moderate prevalence among European countries.
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Affiliation(s)
- David Polo
- Department of Microbiology and Parasitology, CIBUS-Faculty of Biology & CRETUS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Alberto Lema
- Department of Microbiology and Parasitology, CIBUS-Faculty of Biology & CRETUS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Enia Gándara
- Department of Microbiology and Parasitology, CIBUS-Faculty of Biology & CRETUS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Jesús L Romalde
- Department of Microbiology and Parasitology, CIBUS-Faculty of Biology & CRETUS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
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Xu M, Perdomo MF, Mattola S, Pyöriä L, Toppinen M, Qiu J, Vihinen-Ranta M, Hedman K, Nokso-Koivisto J, Aaltonen LM, Söderlund-Venermo M. Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection. mBio 2021; 12:e03132-20. [PMID: 33531399 PMCID: PMC7858059 DOI: 10.1128/mbio.03132-20] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/08/2020] [Indexed: 12/11/2022] Open
Abstract
Human bocavirus 1 (HBoV1), a nonenveloped single-stranded DNA parvovirus, causes mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children. HBoV1 often persists in nasopharyngeal secretions for months, hampering diagnosis. It has also been shown to persist in pediatric palatine and adenoid tonsils, which suggests that lymphoid organs are reservoirs for virus spread; however, the tissue site and host cells remain unknown. Our aim was to determine, in healthy nonviremic children with preexisting HBoV1 immunity, the adenotonsillar persistence site(s), host cell types, and virus activity. We discovered that HBoV1 DNA persists in lymphoid germinal centers (GCs), but not in the corresponding tonsillar epithelium, and that the cell types harboring the virus are mainly naive, activated, and memory B cells and monocytes. Both viral DNA strands and both sides of the genome were detected, as well as infrequent mRNA. Moreover, we showed, in B-cell and monocyte cultures and ex vivo tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). This resulted in viral mRNA transcription, known to occur exclusively from double-stranded DNA in the nucleus, however, with no detectable productive replication. Confocal imaging with fluorescent virus-like particles moreover disclosed endocytosis. To which extent the active HBoV1 GC persistence has a role in chronic inflammation or B-cell maturation disturbances, and whether the virus can be reactivated, will be interesting topics for forthcoming studies.IMPORTANCE Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown. Our study provides new insights into tonsillar HBoV1 persistence. We observed HBoV1 persistence exclusively in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In cultured cell lines and primary tonsillar B cells, we showed the virus uptake to be significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis, but without detectable productive replication. Possible implications of such active viral persistence could be tonsillar inflammation, disturbances in immune maturation, reactivation, or cell death with release of virus DNA, explaining the long-lasting HBoV1 airway shedding.
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Affiliation(s)
- Man Xu
- Department of Virology, University of Helsinki, Helsinki, Finland
| | | | - Salla Mattola
- Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland
- Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland
| | - Lari Pyöriä
- Department of Virology, University of Helsinki, Helsinki, Finland
| | - Mari Toppinen
- Department of Virology, University of Helsinki, Helsinki, Finland
| | - Jianming Qiu
- Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Maija Vihinen-Ranta
- Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland
- Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland
| | - Klaus Hedman
- Department of Virology, University of Helsinki, Helsinki, Finland
- Helsinki University Hospital, Helsinki, Finland
| | - Johanna Nokso-Koivisto
- Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland
- University of Helsinki, Helsinki, Finland
| | - Leena-Maija Aaltonen
- Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland
- University of Helsinki, Helsinki, Finland
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Al Bishawi A, Ben Abid F, Ibrahim W. Bocavirus Infection in a Young Pregnant Woman: A Case Report and Literature Review. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e928099. [PMID: 33436535 PMCID: PMC7811980 DOI: 10.12659/ajcr.928099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Human bocavirus (HBoV) is a parvovirus found primarily in children and was first identified in 2005. It usually causes mild upper- and lower-respiratory tract infections. HBoV infection seems to be rare during adulthood, probably due to high antibody titers resulting from childhood infection and seroconversion. The clinical significance, possible complications, and consequences of an adulthood infection are still unclear. Furthermore, the consequences of HBoV infection during pregnancy are seldom reported in the literature. CASE REPORT We report the case of a 22-year-old pregnant woman in her third trimester who presented with a 1-week history of fever and cough followed by progressive shortness of breath. She was treated initially as a case of severe pneumonia; however, her condition deteriorated rapidly, resulting in hypoxic respiratory failure that required intensive care support. The patient was found to have dilated cardiomyopathy on echocardiography, and her fetal ultrasound showed no fetal heart activity; subsequently, labor induction for stillbirth was performed. An extensive workup for an underlying cause was unrevealing apart from positive respiratory viral PCR assay for human bocavirus, performed twice. A provisional diagnosis of HBoV pneumonia complicated by dilated cardiomyopathy, stillbirth, and multiorgan failure was made. Fortunately, the patient had a good recovery and was discharged home in good clinical condition. CONCLUSIONS In addition to severe pneumonia, HBoV infection may result in other life-threatening complications. Although the infection is rare during adulthood, infection in a pregnant woman should be taken seriously and close monitoring of such patients is advised.
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Affiliation(s)
- Ahmad Al Bishawi
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Department of Medicine, Division of General Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Fatma Ben Abid
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College, Doha, Qatar
| | - Wanis Ibrahim
- Department of Medicine, Division of General Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College, Doha, Qatar
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Abstract
Parvoviruses are structurally simple viruses with linear single-stranded DNA genomes and nonenveloped icosahedral capsids. They infect a wide range of animals from insects to humans. Parvovirus B19 is a long-known human pathogen, whereas adeno-associated viruses are nonpathogenic. Since 2005, many parvoviruses have been discovered in human-derived samples: bocaviruses 1-4, parvovirus 4, bufavirus, tusavirus, and cutavirus. Some human parvoviruses have already been shown to cause disease during acute infection, some are associated with chronic diseases, and others still remain to be proven clinically relevant-or harmless commensals, a distinction not as apparent as it might seem. One initially human-labeled parvovirus might not even be a human virus, whereas another was originally overlooked due to inadequate diagnostics. The intention of this review is to follow the rocky road of emerging human parvoviruses from discovery of a DNA sequence to current and future clinical status, highlighting the perils along the way.
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Tang YW, Stratton CW. The Role of the Human Bocavirus (HBoV) in Respiratory Infections. ADVANCED TECHNIQUES IN DIAGNOSTIC MICROBIOLOGY 2018. [PMCID: PMC7120174 DOI: 10.1007/978-3-319-95111-9_12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The human bocavirus is one of the most common respiratory viruses and occurs in all age groups. Because Koch’s postulates have been fulfilled unintendedly, it is currently accepted that the virus is a real pathogen associated with upper and lower respiratory tract infections causing clinical symptoms ranging from a mild common cold to life-threatening respiratory diseases. In order to exclude a viremia, serological analysis should be included during laboratory diagnostics, as acute and chronic infections cannot be differentiated by detection of viral nucleic acids in respiratory specimen alone due to prolonged viral shedding. Besides its ability to persist, the virus appears to trigger chronic lung disease and increases clinical symptoms by causing fibrotic lung diseases. Due to the lack of an animal model, clinical trials remain the major method for studying the long-term effects of HBoV infections.
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Affiliation(s)
- Yi-Wei Tang
- Departments of Laboratory Medicine and Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA
| | - Charles W. Stratton
- Department of Pathology, Microbiology and Immunology and Medicine, Vanderbilt University Medical Center, Nashville, TN USA
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9
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Schlaberg R, Ampofo K, Tardif KD, Stockmann C, Simmon KE, Hymas W, Flygare S, Kennedy B, Blaschke A, Eilbeck K, Yandell M, McCullers JA, Williams DJ, Edwards K, Arnold SR, Bramley A, Jain S, Pavia AT. Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia. J Infect Dis 2017; 216:688-696. [PMID: 28934425 PMCID: PMC5853397 DOI: 10.1093/infdis/jix352] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 07/19/2017] [Indexed: 12/14/2022] Open
Abstract
Background The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. Methods As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. Results HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0–2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6–26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5–38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6–2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9–82]) was strongly associated with CAP. Conclusions Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing.
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Affiliation(s)
- Robert Schlaberg
- Department of Pathology.,ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah
| | | | - Keith D Tardif
- ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah
| | | | | | - Weston Hymas
- ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah
| | | | | | | | | | - Mark Yandell
- Department of Human Genetics, University of Utah
| | - Jon A McCullers
- Department of Pediatrics, University of Tennessee Health Sciences Center.,Nashville and Le Bonheur Children's Hospital.,St. Jude Children's Research Hospital, Memphis
| | - Derek J Williams
- Vanderbilt University School of Medicine.,Division of Infectious Diseases, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University.,Vanderbilt Vaccine Research Program, Nashville, Tennessee
| | - Kathryn Edwards
- Division of Infectious Diseases, Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Vanderbilt University.,Vanderbilt Vaccine Research Program, Nashville, Tennessee
| | - Sandra R Arnold
- Department of Pediatrics, University of Tennessee Health Sciences Center.,Nashville and Le Bonheur Children's Hospital
| | - Anna Bramley
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Seema Jain
- Centers for Disease Control and Prevention, Atlanta, Georgia
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De R, Liu L, Qian Y, Zhu R, Deng J, Wang F, Sun Y, Dong H, Jia L, Zhao L. Risk of acute gastroenteritis associated with human bocavirus infection in children: A systematic review and meta-analysis. PLoS One 2017; 12:e0184833. [PMID: 28910409 PMCID: PMC5599015 DOI: 10.1371/journal.pone.0184833] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 08/31/2017] [Indexed: 01/10/2023] Open
Abstract
Human bocaviruses (HBoVs), which were first identified in 2005 and are composed of genotypes 1–4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. To investigate if HBoV infection is a risk factor of acute gastroenteritis in children younger than 5 years old, we searched PubMed, Embase (via Ovid), the Chinese Biomedical Literature Database (CBM), and the Cochrane Library for studies assessing the prevalence of HBoVs in individuals from Oct 25, 2005 to Oct 31, 2016. We included studies using PCR-based diagnostics for HBoVs from stool specimens of patients with or without acute gastroenteritis that carried out research for over 1 year on pediatric patients aged younger than 5 years old. The primary outcome was the HBoV prevalence among all cases with acute gastroenteritis. Pooled estimates of the HBoV prevalence were then generated by fitting linear mixed effect meta-regression models. Of the 36 studies included, the pooled HBoV prevalence in 20,591 patients with acute gastroenteritis was 6.90% (95% confidence interval (95% CI): 5.80–8.10%). In the ten studies with a control group, HBoVs were detected in 12.40% of the 3,620 cases with acute gastroenteritis and in 12.22% of the 2,030 control children (odds ratio (OR): 1.44; 95% CI: 0.95–2.19, p = 0.09 between case and control groups). HBoV1 and HBoV2 were detected in 3.49% and 8.59% of acute gastroenteritis cases, respectively, and in 2.22% and 5.09% of control children, respectively (OR: 1.40; 95% CI: 0.61–3.25; p = 0.43 and OR: 1.68; 95% CI: 1.21–2.32; p = 0.002, respectively). Current evidence suggests that the overall HBoV prevalence in children younger than 5 years old is not significantly different between groups with or without acute gastroenteritis. However, when HBoV1 was excluded, the HBoV2 prevalence was significantly different between these two groups, which may imply that HBoV2 is a risk factor of acute gastroenteritis in children younger than 5 years old.
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Affiliation(s)
- Ri De
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Liying Liu
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Yuan Qian
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Runan Zhu
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Jie Deng
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Fang Wang
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Yu Sun
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Huijin Dong
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Liping Jia
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
| | - Linqing Zhao
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China
- * E-mail:
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Abstract
Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology.
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Affiliation(s)
- Jianming Qiu
- Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA
| | | | - Neal S Young
- Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
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12
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Guido M, Tumolo MR, Verri T, Romano A, Serio F, De Giorgi M, De Donno A, Bagordo F, Zizza A. Human bocavirus: Current knowledge and future challenges. World J Gastroenterol 2016; 22:8684-8697. [PMID: 27818586 PMCID: PMC5075545 DOI: 10.3748/wjg.v22.i39.8684] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 08/30/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.
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Jiang W, Yin F, Zhou W, Yan Y, Ji W. Clinical significance of different virus load of human bocavirus in patients with lower respiratory tract infection. Sci Rep 2016; 6:20246. [PMID: 26832453 PMCID: PMC4735282 DOI: 10.1038/srep20246] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 12/31/2015] [Indexed: 12/23/2022] Open
Abstract
To assess the impact of human bocavirus (HBoV) virus load on epidemiologic and clinical characteristics in children with lower respiratory tract infection (LRTI). Clinical records of a total of 654 patients with HBoV infection during January 2013 and December 2014 were retrospectively reviewed. Patients with high HBoV virus load infection had a similar age distribution with the total HBoV infection, which had a peak age group of 6–24 months. Patients with high virus load are significantly younger (P < 0.01) than those with low load. The patients who had wheeze and tachypnea/dyspnea at presentation were more strongly affiliated with the patients with high virus load (both P < 0.01). Co-infection was found significantly more frequently among patients with low virus load than those with high virus load (57.0% vs 38.9%; P < 0.01). High virus load was a significant predictor of severe LRTI (P < 0.05). HBoV infections are found in an important proportion of the hospitalized children with respiratory illnesses (8.85% in our series). A high HBoV virus load could be an etiologic agent for LRTI, which may lead to more severe lower respiratory tract symptom and severe disease.
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Affiliation(s)
- Wujun Jiang
- Department of Respiratory Medicine, Children's Hospital of Soochow University, Soochow University, Suzhou, China
| | - Fang Yin
- Department of Pediatrics, People's Hospital of Weifang, Weifang, China
| | - Weifang Zhou
- Department of Infectious Disease, Children's Hospital of Soochow University, Soochow University, Suzhou, China
| | - Yongdong Yan
- Department of Respiratory Medicine, Children's Hospital of Soochow University, Soochow University, Suzhou, China
| | - Wei Ji
- Department of Respiratory Medicine, Children's Hospital of Soochow University, Soochow University, Suzhou, China
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Schildgen O, Schildgen V. Respiratory infections of the human bocavirus. THE MICROBIOLOGY OF RESPIRATORY SYSTEM INFECTIONS 2016. [PMCID: PMC7149820 DOI: 10.1016/b978-0-12-804543-5.00005-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The human bocavirus is one of the most common respiratory viruses and occurs in all age groups. It is associated with upper and lower respiratory tract infections, and causes clinical symptoms from the mild common cold to life threatening respiratory diseases. Besides its ability to persist the virus appears to trigger chronic lung disease and increase the clinical symptoms, while being a putative trigger for fibrotic lung diseases. Laboratory diagnostics should include serological diagnostics in order to rule out a viremia because due to prolonged viral shedding acute and chronic infections cannot be differentiated on the detection of viral nucleic acids in respiratory specimen alone. Although Koch’s postulates cannot be formally fulfilled due to the lack of an animal model and the chance for clinical trials with volunteers are limited due to the long term effects of HBoV infections, there is no doubt that the virus is a serious pathogen and requires attention. The aim of the chapter is to present an overview of our current knowledge on respiratory infections with the human bocavirus, and to provide basic and essential information on clinical features, molecular diagnostics, and epidemiologic challenges arising with this pathogen.
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Günel C, Kırdar S, Ömürlü İK, Ağdaş F. Detection of the Epstein-Barr virus, Human Bocavirus and novel KI and KU polyomaviruses in adenotonsillar tissues. Int J Pediatr Otorhinolaryngol 2015; 79:423-7. [PMID: 25631935 DOI: 10.1016/j.ijporl.2015.01.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 01/07/2015] [Accepted: 01/08/2015] [Indexed: 01/30/2023]
Abstract
OBJECTIVES We aimed to investigate the seasonal disturbations and the rates of detection of Epstein-Barr virus (EBV), Human Bocavirus (HBoV), and polyomaviruses KI and WU (KIPyV and WUPyV) in adenoid and tonsil tissues during the absence of acute infection symptoms. STUDY DESIGN Cross-sectional prospective study. SETTING Tertiary hospital. METHODS DNA expressions of EBV, HBoV, polyomaviruses KIPyV and WUPyV were investigated in children with chronic tonsillar and adenoidal diseases using real-time polymerase chain reaction. The patients were grouped as follows: adenoid, recurrent tonsillitis and hypertrophic tonsillitis group. The relationships of the expressions of these viruses with age, gender, recurrent infection and airway obstruction were also analyzed. Seasonal variations in rates of detection of these viruses in adenoid and tonsil tissues were also investigated. RESULTS Considering adenoid specimens, HBoV was found to be the most frequent virus with the rate of 43.1%. In specimens of recurrent tonsillitis and hypertrophic tonsils, EBV was the most frequently encountered virus (53.8%, and 32.0%, respectively). In children with hypertrophic adenoids, while HBoV was detected to be positive throughout the year, EBV was present throughout the year in children with recurrent tonsillitis. CONCLUSIONS The detection of HBoV and EBV throughout the year in samples of children with asymptomatic chronic adenotonsillar diseases may indicate that these viruses may remain persistently in lymphoepithelial tissues of upper respiratory tract. Virus persistence may have a pathogenetic potential for development of lymphoid hypertrophy and a chronic stimulatory effect for inflammation.
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Affiliation(s)
- Ceren Günel
- Adnan Menderes Üniversity Faculty of Medicine, Department of Otorhinolaryngology Head and Neck Surgery, Aydın, Turkey.
| | - Sevin Kırdar
- Adnan Menderes Üniversity, Faculty of Medicine, Department of Medical Microbiology, Aydın, Turkey.
| | - İmran Kurt Ömürlü
- Adnan Menderes Üniversity, Faculty of Medicine, Department of Bioistatistic, Aydın, Turkey.
| | - Fatih Ağdaş
- Adnan Menderes Üniversity Faculty of Medicine, Department of Otorhinolaryngology Head and Neck Surgery, Aydın, Turkey.
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Abstract
Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.
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Abstract
Non-influenza respiratory virus infections are common worldwide and contribute to morbidity and mortality in all age groups. The recently identified Middle East respiratory syndrome coronavirus has been associated with rapidly progressive pneumonia and high mortality rate. Adenovirus 14 has been increasingly recognized in severe acute respiratory illness in both military and civilian individuals. Rhinovirus C and human bocavirus type 1 have been commonly detected in infants and young children with respiratory tract infection and studies have shown a positive correlation between respiratory illness and high viral loads, mono-infection, viremia, and/or serologically-confirmed primary infection.
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Affiliation(s)
- James J Dunn
- Department of Pathology and Laboratory Medicine, Cook Children's Medical Center, 801 Seventh Avenue, Fort Worth, TX 76104, USA.
| | - Melissa B Miller
- Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Campus Box 7525, Chapel Hill, NC 27599-7525, USA
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Nokso-Koivisto J, Pyles RB, Miller AL, Jennings K, Loeffelholz M, Chonmaitree T. Role of Human Bocavirus in Upper Respiratory Tract Infections and Acute Otitis Media. J Pediatric Infect Dis Soc 2014; 3:98-103. [PMID: 26625362 PMCID: PMC4865000 DOI: 10.1093/jpids/pit061] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Accepted: 06/30/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Human bocavirus (HBoV) is a newly described parvovirus. HBoV1 has been associated with respiratory infections, including acute otitis media (AOM), but the knowledge on the significance of HBoV1 in upper respiratory tract infections (URI) and AOM in relation to other respiratory viruses is limited. The objective of this study was to compare the rate of detection of HBoV1 to that of other respiratory viruses in specimens from children with URI, with and without AOM complication. METHODS Nasopharyngeal secretions (NPS) were collected during URI from healthy children (6-35 months) followed prospectively for 1 year; specimens have been previously analyzed for broad spectrum of respiratory viruses. Archived NPS were analyzed for HBoV1 using a high-throughput, quantitative polymerase chain reaction method. RESULTS Seven hundred and seven NPS samples collected during URI episodes from 201 children were studied for HBoV1. A total of 94 (47%) children tested positive for HBoV1 DNA during 172 (24%) URI episodes; HBoV1 was present as the only virus in 44 (6%) URI episodes. Overall, 37% of URI episodes were complicated by AOM. Of URI associated with single virus (n = 303), the rate of AOM complicating URI associated with HBoV1 only was 52% (23 of 44); this was a higher AOM rate, compared to that of other respiratory viruses. CONCLUSIONS Among URI associated with single respiratory virus, HBoV1-URI was commonly associated with AOM complication. The important role of HBoV1 on AOM pathogenesis needs to be studied further.
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Affiliation(s)
| | - Richard B. Pyles
- Department of Pediatrics
- Department of Microbiology and Immunology
| | | | | | | | - Tasnee Chonmaitree
- Department of Pediatrics
- Department of Pathology, University of Texas Medical Branch, Galveston
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Biill Primo OV, Lourenço EA, Passos SD. Detection of respiratory viruses in nasopharyngeal swab and adenoid tissue from children submitted to adenoidectomy: pre- and postoperative analysis. Int Arch Otorhinolaryngol 2014; 18:150-4. [PMID: 25992082 PMCID: PMC4296995 DOI: 10.1055/s-0034-1368135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 12/02/2013] [Indexed: 11/25/2022] Open
Abstract
Introduction The presence of respiratory viruses in lymphoid tissues of the nasopharynx and oropharynx and its impact on recurrent infections and hypertrophy of these tissues are not yet fully understood. Objective To identify and determine the prevalence of major respiratory viruses in nasopharyngeal secretions and adenoid tissue pre- and postoperatively of children undergoing adenoidectomy. Methods A prospective observational study was conducted in 36 patients under 12 years of age with upper airway lymphoid hypertrophy who were undergoing adenoidectomy, in which various respiratory viruses were investigated using real-time polymerase chain reaction in adenoid tissue and nasopharyngeal secretions collected preoperatively and 30 days postoperatively. Results At least 1 viral agent was isolated in any of the samples collected in 58.3% of children and 25.9% of total samples. Respiratory viruses were identified in 33.8% of preoperative nasopharyngeal specimens and in 19.8% of postoperative secretion. Of the 21 patients with positive results for any respiratory virus, 6 (28.6%) had more than 1 virus. Considering all 36 respiratory viruses found, the main agent isolated was rhinovirus (27.8%), followed by bocavirus (22.2%). Conclusion The virus found more frequently in all samples was rhinovirus. After removal of adenoid tissue, there was a decrease in the prevalence of the virus contained in nasopharyngeal secretion 30 days after surgery.
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Affiliation(s)
| | - Edmir Américo Lourenço
- Department of Otorhinolaryngology, Faculdade de Medicina de Jundiaí, Jundiaí, São Paulo, Brazil
| | - Saulo Duarte Passos
- Department of Pediatrics, Faculdade de Medicina de Jundiaí, Jundiaí, São Paulo, Brazil
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Norja P, Hedman L, Kantola K, Kemppainen K, Suvilehto J, Pitkäranta A, Aaltonen LM, Seppänen M, Hedman K, Söderlund-Venermo M. Occurrence of human bocaviruses and parvovirus 4 in solid tissues. J Med Virol 2012; 84:1267-73. [PMID: 22711355 DOI: 10.1002/jmv.23335] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology.
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Affiliation(s)
- Päivi Norja
- Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland.
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Proenca-Modena JL, Pereira Valera FC, Jacob MG, Buzatto GP, Saturno TH, Lopes L, Souza JM, Paula FE, Silva ML, Carenzi LR, Tamashiro E, Arruda E, Anselmo-Lima WT. High rates of detection of respiratory viruses in tonsillar tissues from children with chronic adenotonsillar disease. PLoS One 2012; 7:e42136. [PMID: 22870291 PMCID: PMC3411673 DOI: 10.1371/journal.pone.0042136] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 07/02/2012] [Indexed: 11/23/2022] Open
Abstract
Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.
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Affiliation(s)
- Jose Luiz Proenca-Modena
- Department of Cell Biology, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Fabiana Cardoso Pereira Valera
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Marcos Gerhardinger Jacob
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Guilherme Pietrucci Buzatto
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Tamara Honorato Saturno
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Lucia Lopes
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Jamila Mendonça Souza
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Flavia Escremim Paula
- Department of Cell Biology, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Maria Lucia Silva
- Department of Cell Biology, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Lucas Rodrigues Carenzi
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Edwin Tamashiro
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Eurico Arruda
- Department of Cell Biology, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
- Virology Research Center, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
| | - Wilma Terezinha Anselmo-Lima
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirao Preto of University of São Paulo, Ribeirao Preto, Brazil
- * E-mail:
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Schildgen O, Qiu J, Söderlund-Venermo M. Genomic features of the human bocaviruses. Future Virol 2012; 7:31-39. [PMID: 22389649 DOI: 10.2217/fvl.11.136] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The human bocavirus (HBoV) was initially discovered in 2005 as the second pathogenic member of the parvovirus family, next to the human parvovirus B19. HBoV has since been shown to be extremely common worldwide and to cause a systemic infection in small children often resulting in respiratory disease. Three more, presumably enteric, human bocaviruses (HBoV2-4) have been identified in stool samples. Parvoviruses are assumed to replicate via their genomic terminal hairpin-like structures in a so-called 'rolling-hairpin model'. These terminal sequences have recently been partially identified in head-to-tail HBoV-PCR amplicons from clinical samples, and are most likely hybrid relics of HBoV's predecessors, namely bovine parvovirus 1 on the left-hand side and minute virus of canines on the right, shown for the first time in this article. Thereby, the replication model postulated for HBoV remains questionable as the occurrence of head-to-tail sequences is not a typical feature of the rolling-hairpin replication model. However, such episomes can also be persistent storage forms of the genome.
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Affiliation(s)
- Oliver Schildgen
- Institut für Pathologie, Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke, Cologne, Germany
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Falcone V, Ridder GJ, Panning M, Bierbaum S, Neumann-Haefelin D, Huzly D. Human bocavirus DNA in paranasal sinus mucosa. Emerg Infect Dis 2011; 17:1564-5. [PMID: 21801654 PMCID: PMC3381581 DOI: 10.3201/eid1708.101944] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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Jartti T, Hedman K, Jartti L, Ruuskanen O, Allander T, Söderlund-Venermo M. Human bocavirus-the first 5 years. Rev Med Virol 2011; 22:46-64. [PMID: 22038931 DOI: 10.1002/rmv.720] [Citation(s) in RCA: 188] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Revised: 09/17/2011] [Accepted: 09/19/2011] [Indexed: 12/17/2022]
Abstract
Four species of human bocavirus (HBoV) have been recently discovered and classified in the Bocavirus genus (family Parvoviridae, subfamily Parvovirinae). Although detected both in respiratory and stool samples worldwide, HBoV1 is predominantly a respiratory pathogen, whereas HBoV2, HBoV3, and HBoV4 have been found mainly in stool. A variety of signs and symptoms have been described in patients with HBoV infection including rhinitis, pharyngitis, cough, dyspnea, wheezing, pneumonia, acute otitis media, fever, nausea, vomiting, and diarrhea. Many of these potential manifestations have not been systematically explored, and they have been questioned because of high HBoV co-infection rates in symptomatic subjects and high HBoV detection rates in asymptomatic subjects. However, evidence is mounting to show that HBoV1 is an important cause of lower respiratory tract illness. The best currently available diagnostic approaches are quantitative PCR and serology. This concise review summarizes the current clinical knowledge on HBoV species.
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Affiliation(s)
- Tuomas Jartti
- Department of Pediatrics, Turku University Hospital, Turku, Finland.
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25
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Malecki M, Schildgen V, Schildgen O. Human bocavirus: still more questions than answers. Future Virol 2011. [DOI: 10.2217/fvl.11.78] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The human bocavirus was first detected in 2005 and since then has been found in both respiratory secretions from patients with airway infections and in stool samples from patients with gastroenteritis. Meanwhile, four different genotypes have been identified that most likely derive from recombination events. Although the modified Koch’s postulates have not yet been fulfilled completely, owing to the lack of an animal model or a simple cell culture system, there is increasing evidence that the human bocaviruses are serious participants in infectious diseases of the respiratory and the GI tracts. This article reviews the current status of the clinical features of human bocaviruses and provides an overview of the latest findings concerning the biology, phylogeny, epidemiology and diagnostic tools related to human bocaviruses. Furthermore, it discusses the potential pathogenicity of human bocavirus, as well as its persistence and reactivation in hosts.
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Affiliation(s)
- Monika Malecki
- Kliniken der Stadt Köln gGmbH, Krankenhaus Merheim, Klinikum der Privaten Universität Witten/Herdecke, Institut für Pathologie, Ostmerheimer Str. 200, D-51109 Cologne, Germany
| | - Verena Schildgen
- Kliniken der Stadt Köln gGmbH, Krankenhaus Merheim, Klinikum der Privaten Universität Witten/Herdecke, Institut für Pathologie, Ostmerheimer Str. 200, D-51109 Cologne, Germany
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Streiter M, Malecki M, Prokop A, Schildgen V, Lüsebrink J, Guggemos A, Wisskirchen M, Weiss M, Cremer R, Brockmann M, Schildgen O. Does human bocavirus infection depend on helper viruses? A challenging case report. Virol J 2011; 8:417. [PMID: 21871135 PMCID: PMC3179752 DOI: 10.1186/1743-422x-8-417] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 08/29/2011] [Indexed: 12/21/2022] Open
Abstract
A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.
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Affiliation(s)
- Monika Streiter
- Klinik für Kinder- und Jugendmedizin, Kinderkrankenhaus, Kliniken der Stadt Köln gGmbH, Amsterdamer Str. 59, Cologne 50735, Germany
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Detection of human bocavirus mRNA in respiratory secretions correlates with high viral load and concurrent diarrhea. PLoS One 2011; 6:e21083. [PMID: 21701591 PMCID: PMC3118811 DOI: 10.1371/journal.pone.0021083] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2011] [Accepted: 05/18/2011] [Indexed: 12/31/2022] Open
Abstract
Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>108 copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections.
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McErlean P, Greiman A, Favoreto S, Avila PC. Viral diversity in asthma. Immunol Allergy Clin North Am 2011; 30:481-95, v. [PMID: 21029933 PMCID: PMC2967440 DOI: 10.1016/j.iac.2010.08.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Peter McErlean
- Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, 240 East Huron, McGaw M530h, Chicago, IL 60611, USA.
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Azoulay E. Emerging Viral Infections. PULMONARY INVOLVEMENT IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES 2011. [PMCID: PMC7123354 DOI: 10.1007/978-3-642-15742-4_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Elie Azoulay
- Service de Réanimation Médicale, Hôpital Saint Louis, Avenue Claude Vellefaux 1, Paris, 75010 France
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Abstract
Human bocavirus is frequently detected in immunocompetent as well as in immunocompromised children. However, the course of infection in immunocompromised children is still poorly investigated. In the present study, we describe 4 cases of repeat human bocavirus detection in the presence of severe immunodeficiency. In the view of homologous viral sequences identified in serial samples, possible persistence and reactivation in these patients are discussed.
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Respiratory Viral Infections. TROPICAL INFECTIOUS DISEASES: PRINCIPLES, PATHOGENS AND PRACTICE 2011. [PMCID: PMC7149827 DOI: 10.1016/b978-0-7020-3935-5.00058-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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32
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Affiliation(s)
- John V. Williams
- Departments of Pediatrics and Microbiology and Immunology Vanderbilt University School of Medicine and the Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville Tennessee
- Reprints or correspondence: Dr John V. Williams Pediatric Infectious Diseases Vanderbilt University Medical Center D7235 Medical Center North 1161 21st Ave South Nashville TN 37232–2581 ()
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33
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Affiliation(s)
- Brian D W Chow
- Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
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Clément N, Battaglioli G, Jensen RL, Schnepp BC, Johnson PR, St George K, Linden RM. Prevalence of human bocavirus in human tonsils and adenoids. Emerg Infect Dis 2009; 15:1149-50. [PMID: 19624951 PMCID: PMC2744251 DOI: 10.3201/eid1507.090102] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Frequent detection of respiratory viruses by real-time PCR in adenoid samples from asymptomatic children. J Clin Microbiol 2009; 47:2682-3. [PMID: 19494063 DOI: 10.1128/jcm.00899-09] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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36
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Abstract
Several new viruses have recently been described in children, including human metapneumovirus (hMPV) and human bocavirus (HBoV). hMPV has been established as a common cause of upper and lower respiratory tract infections in children, often second only to respiratory syncytial virus as a cause of bronchiolitis in infants. Diagnostic tools have been developed for the clinician and effective treatment and prevention strategies are being investigated. HBoV was more recently identified. Although it was initially identified in the airway of children, high rates of codetection of other viral pathogens and detection of the virus in the stool have raised questions about the true role of HBoV as a cause of respiratory infections. A focus on epidemiology, pathogenesis, clinical features, and diagnostic techniques for hMPV and HBoV is presented.
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Affiliation(s)
- Edmund Milder
- Department of Pediatrics, Naval Medical Center, San Diego, California 92134, USA
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Lüsebrink J, Wittleben F, Schildgen V, Schildgen O. Human bocavirus - insights into a newly identified respiratory virus. Viruses 2009; 1:3-12. [PMID: 21994534 PMCID: PMC3185462 DOI: 10.3390/v1010003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2009] [Revised: 04/16/2009] [Accepted: 04/20/2009] [Indexed: 12/26/2022] Open
Abstract
Human Bocavirus (HBoV) was discovered in 2005 using a molecular virus screening technique. It is often found in respiratory samples and is a likely cause for respiratory diseases in children. HBoV is distributed worldwide and has been found not only in respiratory samples, but also in feces, urine and serum. HBoV infections are mostly found in young children and coinfections with other respiratory viruses are often found, exacerbating the efforts to link HBoV to specific symptoms. The purpose of this review is to give an overview of recent HBoV research, highlighting some recent findings.
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Affiliation(s)
| | | | | | - Oliver Schildgen
- Author to whom correspondence should be addressed; E-mails: or ; Tel.: +49-228-28711186
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Abstract
Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). In this study, human tonsil and adenoid tissues were analyzed to determine the dynamics of infection, the rate of clearance of viral DNA, and the possibility of reactivation of virus from these tissues. The presence of viral DNA peaked at 4 years of age and declined thereafter. The average number of viral genomes declined with the age of the donor. The frequency of virus-bearing cells ranged from 3 x 10(-7) to 3.4 x 10(-4), while the amount of viral DNA per cell varied less, with an average of 280 copies per cell. All species C serotypes were represented in these tissues, although adenovirus type 6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested), even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation. These data suggest that species C adenoviruses can establish latent infections in mucosal lymphocytes and that stimulation of these cells can cause viral reactivation resulting in RNA transcription, DNA replication, and infectious virus production.
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