Medline was searched for papers in the English language using the terms “BKV”, “BK virus”, “polyomavirus”, and “polyoma”. For specific sections, search terms were combined with “immunodeficiency”, “HIV”, and “transplantation”. Abstracts of the most recent meetings were reviewed such as the American Transplant Congress, the American Society of Nephrology Congress, and the Interscience Conference on Antimicrobial Agents and Chemotherapy. Articles were selected according to the documented or
ReviewPolyomavirus BK
Section snippets
BKV virology
BKV, JCV, and the simian virus SV40 are species of the genus polyomavirus within the polyomaviridae, a family of unenveloped DNA viruses with icosahedral capsids of 45 μm diameter (figure 1). The capsids contain the viral genomes, circular double-stranded DNA of 5300 base pairs (bp) coated by host-cell histones. The BKV genome shares an overall homology of 75% with JCV and of 70% with SV40, and can be divided into regulatory, early, and late region. After virion uptake by endocytosis of
BKV infection, replication, and disease
High prevalence and symptomless reactivation have impeded a clear appreciation of the pathogenic role of BKV. For the purpose of this review, BKV infection, replication, and disease were defined as shown in the panel.
BKV epidemiology
Serological studies indicate that primary BKV infection occurs independently of JCV during childhood at a median age of 4–5 years.14, 15 The seroprevalence is lowest at the age of 6 months after the loss of maternal antibodies and increases to about 75% among adults worldwide (range 46–94%) except for some remote populations in South America and Asia.15 After primary infection, BKV persists in the renourinary tract as the principal site.16 Thus, viraemic spread from the site of entry has to be
BKV transmission
The natural route of transmission has not been established. Serological association of primary infection with upper respiratory infection suggests transmission via aerosol or fomites.22, 23 Urinary shedding argues for oral transmission by contaminated food, water, or smear infection.24 Archetypical strains have been detected in sewage and shellfish samples around the world.25, 26 Transplacental transmission has been proposed based on the detection of IgM in cord blood samples and of BKV DNA by
BKV immunity and reactivation
The innate and adaptive immune response to BKV is little investigated. The JCV—independent increase of BKV seroprevalence during childhood provides evidence for high specificity.14 The humoral immune response consists of IgG, IgM, and IgA, which includes neutralising and subtypespecific antibodies directed against determinants on the BKV major capsid protein VP1.15 The presence of LT—agspecific antibodies indicates that not only virions, but also remnants of infected cells are processed by
Patterns of polyomavirus disease
The pathogenetic role of BKV infection may differ depending on the clinical setting. In a simplistic approach, polyomavirus disease could be divided into different patterns.
Determinants and modulators of BKV disease
BKV disease is likely to depend on multiple, partly complementing risk factors (figure 2).54 Host determinants include BKV serostatus, quality and quantity of immune effectors, and age. Organ determinants include permissiveness for BKV replication, immunological, or toxic injury. Potential viral determinants are serological and replicative characteristics. These determinants and their interaction are affected by rather dynamic dose–dependent and magnitude–dependent modulators such as
Manifestations in immunocompetent individuals
Conceptually, BKV replication in an immunocompetent individual would be most likely to cause disease when the immune effectors are naive as during primary infection. Primary BKV infection is poorly characterised, presumably because of its subclinical or unspecific “flu-like” course. Serological evidence implicated primary BKV infection in 1–20% of children with upper-respiratory-tract symptoms, fever, or malaise.22, 23 BKV genome sequences have been detected by hybridisation in tonsillar tissue
Manifestations in inherited immune dysfunction
Inherited immune dysfunction increases the susceptibility to various infectious complications.60 In two cases, renal failure due to PAN was documented. 42, 43 A 6—year-old boy with hyper-IgM-syndrome (HIM) presented with irreversible renal failure and shedding of decoy cells.42 Renal biopsy showed the by now classic features of PAN (stage B) with multifocal sites of BKV replication and unspecific inflammatory infiltrates. On autopsy 4 months later, progression to diffuse interstitial fibrosis
Manifestations in acquired immune dysfunction
HIV-1 infection represents the most frequent cause of acquired immunodeficiency today. The natural course is characterised by a progressive decline of CD4–cells and lifethreatening opportunistic complications. The major polyomavirus disease in AIDS is JCV-mediated PML affecting 1–6% of patients. Clinical manifestations of BKV in AIDS patients are rare despite frequent reactivation. The prevalence of BKV shedding increases from 4–8% to 27–51% when CD4 cell counts fall below 200/μL, without
Manifestations in therapeutic immune dysfunction
In organ transplantation, suppression of immune responses is indicated to avoid immunological injury and allograft loss. Manifestations of BKV disease may vary according to the transplantation procedures and the corresponding determinants and modulators.
Autoimmune disease and cancer
BKV-specific diagnostic criteria are difficult to establish for malignant transformation or autoimmune disease. BKV may be an innocent bystander, or an initiating lesion that is no longer required for subsequent progression steps (“hit and run”), or may actually support disease activity. BKV infection has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) as one of several potential triggers of an autoimmune response.11 One of the diagnostic hallmarks of SLE activity is
Conclusion
Development of BKV disease is likely to require complementing determinants in the host, the target organ, and possibly the virus, which are subject to dynamic modulators. These complex aspects are highlighted in PAN, an emerging disease in renal allograft recipients. Despite considerable progress in the past 2 years, present understanding of BKV disease is incomplete and needs further research to ultimately improve patient care. A better definition of risk factors and more effective and less
Search strategy and selection criteria
References (156)
- et al.
New human papovavirus (BK) isolated from urine after transplantation
Lancet
(1971) - et al.
Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy
Lancet
(1971) Polyomavirus BK nephropathy: a (re-) emerging complication in renal transplantation
Am J Transplant
(2002)- et al.
Morphological spectrum of polyoma virus disease in renal allografts: diagnostic accuracy of urine cytology
Am J Transplant
(2001) - et al.
Cynomolgus polyomavirus infection: a new member of the polyoma virus family causes interstitial nephritis, ureteritis, and enteritis in immunosuppressed cynomolgus monkeys
Am J Pathol
(1999) - et al.
Acute hemorrhagic cystitis of childhood and papovavirus-like particles
J Pediatr
(1976) - et al.
Lytic JC virus infection in the kidneys of AIDS subjects
Mod Pathol
(2003) - et al.
BK virus infection in a kidney allograft diagnosed by needle biopsy
Am J Kidney Dis
(1995) - et al.
Polyomavirus in kidney and kidney-pancreas transplantation: a defined protocol for immunosuppression reduction and histologic monitoring
Transplant Proc
(2002) - et al.
Polyomavirus-induced acute tubulo-interstitial nephritis in renal allograft recipients
Transplant Proc
(2000)
BK virus infection in renal allograft recipients
Transplant Proc
Graft dysfunction and polyomavirus infection in renal allograft recipients
Transplant Proc
Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy
Kidney Int
Strains of JC virus in Amerind-speakers of North America (Salish) and South America (Guarani), Na-Dene-speakers of New Mexico (Navajo), and modern Japanese suggest links through an ancestral Asian population
Am J Phys Anthropol
The human polyomaviruses: past, present and future
BK virus nephropathy—polyomavirus adding insult to injury
N Engl J Med
Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss
Transplantation
Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy
Transplantation
Structure and function of the transcriptional control region of nonpassaged BK virus
J Virol
Molecular biology of BK virus and clinical and basic aspectes of BK virus renal infection
Genomic typing of BK virus in clinical specimens by direct sequencing of polymerase chain reaction products
J Med Virol
BK virus antigenic variants: sequence analysis within the capsid VP1 epitope
J Med Virol
High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland
J Infect Dis
The epidemiology of BK Virus and the occurrence of antigenic and genomic subtypes
Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues
J Infect Dis
Detection of human polyomaviruses and papillomaviruses in prostatic tissue reveals the prostate as a habitat for multiple viral infections
Prostate
BK and JC viruses in patients with systemic lupus erythematosus: prevalent and persistent BK viruria, sequence stability of the viral regulatory regions, and nondetectable viremia
J Infect Dis
The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study
J Infect Dis
Polyomavirus persistence in lymphocytes: prevalence in lymphocytes from blood donors and healthy personnel of a blood transfusion centre
J Gen Virol
Latent and persistent polyomavirus infection
The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils
J Med Virol
BK virus specific IgM responses in cord sera, young children and healthy adults detected by RIA
Arch Virol
Detection of BK virus DNA in nasopharyngeal aspirates from children with respiratory infections but not in saliva from immunodeficient and immunocompetent adult patients
J Clin Microbiol
Documenting the epidemiologic patterns of polyomaviruses in human populations by studying their presence in urban sewage
Appl Environ Microbiol
Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA
J Virol
Transplacental transmission of human polyomavirus BK
J Med Virol
A serological investigation of BK virus and JC virus infections in recipients of renal allografts
J Infect Dis
Human polyomavirus BKV and renal disease
Nephrol Dial Transplant
Antibodies to BK virus structural and tumor antigens in human sera from normal persons and from patients with various diseases, including neoplasia
Infect Immun
Cell-mediated immune responses to BK virus in normal individuals
J Med Virol
BK virus specific humoral and cell mediated immunity in allogeneic bone marrow transplant (BMT) recipients
J Med Virol
Activation of human polyomavirus infection-detection by cytologic technics
Am J Clin Pathol
Survey of human polyomavirus (JCV, BKV) infections in 139 patients with lung cancer, breast cancer, melanoma, or lymphoma
Prog Clin Biol Res
BK and JC viruses in human immunodeficiency virus type 1-infected persons: prevalence, excretion, viremia, and viral regulatory regions
J Infect Dis
Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients
J Clin Pathol
Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects
J Infect Dis
Prevalence of long-term BK and JC excretion in HIV-infected adults and lack of correlation with serological markers
J Med Virol
Association of prolonged survival in HLA-A2+progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope
J Immunol
Atypical progressive multifocal leukoencephalopathy with plasma-cell infiltrates
Acta Neuropathol Suppl (Berl)
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Daily low dose intravesical cidofovir for the treatment of BK virus associated hemorrhagic cystitis after allogeneic stem cell transplantation
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