Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors.

BACKGROUND The replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, but the behavior of these viruses in immunocompetent individuals has hardly been characterized. METHODS We used EIA to study samples obtained from 400 healthy blood donors aged 20-59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction. RESULTS IgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20-29 years) to 71% (71 of 100) in the oldest group (aged 50-59 years) (P = .006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P = .06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P < .001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma. CONCLUSIONS Our study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiology.

[1]  R. Munivenkatappa,et al.  Polyomavirus BK Versus JC Replication and Nephropathy in Renal Transplant Recipients: A Prospective Evaluation , 2007, Transplantation.

[2]  M. Battegay,et al.  HIV-1-infected patients with focal neurologic signs: diagnostic role of PCR for Toxoplasma gondii, Epstein-Barr virus, and JC virus. , 1998, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[3]  T. Klimkait,et al.  Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. , 2000, The New England journal of medicine.

[4]  G. Botti,et al.  Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre‐Emptive Intervention in Pediatric Kidney Recipients , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  S. Finkelstein,et al.  Viral regulatory region sequence variations in kidney tissue obtained from patients with BK virus nephropathy. , 2003, Kidney international.

[6]  R. Orentas,et al.  BK Virus‐Specific Antibodies and BKV DNA in Renal Transplant Recipients with BKV Nephritis , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  A. Degener,et al.  Polyomavirus persistence in lymphocytes: prevalence in lymphocytes from blood donors and healthy personnel of a blood transfusion centre. , 2000, The Journal of general virology.

[8]  R. Garcea,et al.  Seroepidemiology of Human Polyomaviruses , 2009, PLoS pathogens.

[9]  Hans H Hirsch,et al.  Rapid dynamics of polyomavirus type BK in renal transplant recipients. , 2006, The Journal of infectious diseases.

[10]  S. Goodman,et al.  Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  V. ter meulen,et al.  Detection of polyoma virus DNA in PML-brain tissue by (in situ) hybridization. , 1979, The Journal of general virology.

[12]  I. Binet,et al.  Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients , 2008, Journal of Translational Medicine.

[13]  H. Hirsch,et al.  Polyomavirus BK after Kidney Transplantation – Role of Molecular and Immunologic Markers , 2009 .

[14]  D. Clifford,et al.  The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: Defining a consensus terminology , 2011, Journal of NeuroVirology.

[15]  A. Lazzarin,et al.  Diagnosis of central nervous system complications in HIV-infected patients: cerebrospinal fluid analysis by the polymerase chain reaction. , 1997, AIDS.

[16]  K. Yuen,et al.  Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation. , 2001, Blood.

[17]  Qin Chen,et al.  Age-Related Urinary Excretion of BK Polyomavirus by Nonimmunocompromised Individuals , 2006, Journal of Clinical Microbiology.

[18]  J. Heritage,et al.  Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. , 1983, The Journal of infectious diseases.

[19]  G. Palù,et al.  Characterization of highly frequent epitope-specific CD45RA+/CCR7+/- T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors , 2006, Journal of Translational Medicine.

[20]  B. Eaton,et al.  BK virus and JC virus shed during pregnancy have predominantly archetypal regulatory regions , 1991, Journal of virology.

[21]  T. Traavik,et al.  BK and JC viruses in human immunodeficiency virus type 1-infected persons: prevalence, excretion, viremia, and viral regulatory regions. , 1994, The Journal of infectious diseases.

[22]  K. Shah,et al.  Serological Cross-Reactivities between Antibodies to Simian Virus 40, BK Virus, and JC Virus Assessed by Virus-Like-Particle-Based Enzyme Immunoassays , 2003, Clinical Diagnostic Laboratory Immunology.

[23]  T. Klimkait,et al.  Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. , 2002, The New England journal of medicine.

[24]  Hans H Hirsch,et al.  Antivirals for the treatment of polyomavirus BK replication , 2007, Expert review of anti-infective therapy.

[25]  F. Ginevri,et al.  Polyomavirus BK Replication Dynamics In Vivo and In Silico to Predict Cytopathology and Viral Clearance in Kidney Transplants , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[26]  E. Major,et al.  T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus. , 2006, The Journal of general virology.

[27]  E. Major,et al.  BK virus antibody titers and intensity of infections after renal transplantation. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[28]  T. Klimkait,et al.  Prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. , 2001, The Journal of infectious diseases.

[29]  E. Major,et al.  Comparison of Antibody Titers Determined by Hemagglutination Inhibition and Enzyme Immunoassay for JC Virus and BK Virus , 2000, Journal of Clinical Microbiology.

[30]  G. Arendt,et al.  Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals , 2011, Journal of NeuroVirology.

[31]  Nina Khanna,et al.  Cytomegalovirus and polyomavirus BK posttransplant. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[32]  F. Barkhof,et al.  Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. , 2006, The New England journal of medicine.

[33]  C. Drachenberg,et al.  Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology , 2008, The Journal of experimental medicine.

[34]  D. Pierson,et al.  The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study. , 2003, The Journal of infectious diseases.

[35]  M. Post,et al.  Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. , 1987, Annals of internal medicine.

[36]  G. Gupta,et al.  Immunoglobulin G, A, and M Responses to BK Virus in Renal Transplantation , 2006, Clinical and Vaccine Immunology.

[37]  C. H. Rinaldo,et al.  Genetic variability in BK Virus regulatory regions in urine and kidney biopsies from renal‐transplant patients , 2006, Journal of medical virology.

[38]  K. Shah,et al.  Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. , 1986, The New England journal of medicine.

[39]  C. Macedo,et al.  Detection of CD8+ T cells sensitized to BK virus large T antigen in healthy volunteers and kidney transplant recipients. , 2006, Human immunology.

[40]  W. Leong,et al.  A prospective study of new infections with herpes simplex virus type 1 and type 2. Chiron HSV Vaccine Study Group. , 1999, The New England journal of medicine.

[41]  H. Hirsch BK virus: opportunity makes a pathogen. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[42]  K. Dörries,et al.  DNA rearrangements in organ-specific variants of polyomavirus JC strain GS , 1988, Journal of virology.

[43]  J. Booth,et al.  Genomic typing of BK virus in clinical specimens by direct sequencing of polymerase chain reaction products , 1993, Journal of medical virology.

[44]  J. Steiger,et al.  Polyomavirus BK. , 2003, The Lancet. Infectious diseases.

[45]  N. Andrews,et al.  Population‐based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40 , 2003, Journal of medical virology.

[46]  H. Hirsch,et al.  Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored , 2007, Clinical and Vaccine Immunology.

[47]  D. Brennan,et al.  Longitudinal Analysis of Levels of Immunoglobulins against BK Virus Capsid Proteins in Kidney Transplant Recipients , 2008, Clinical and Vaccine Immunology.

[48]  J. Cohen,et al.  Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects. , 1993, The Journal of infectious diseases.