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BK, JC, and Other Human Polyomaviruses
Polyomaviruses are a subgroup of small, ubiquitous DNA viruses that belong to the family Papovaviridae. The two most commonly known human polyomaviruses are the BK virus and JC virus, which were first described in 1971. , Subsequently, 12 other human polyomaviruses have been identified. WU polyomavirus and KI polyomavirus in 2007, Merkel cell polyomavirus in 2008, human polyomavirus-6, human polyomavirus-7, and trichodysplasia spinulosa virus in 2010, human polyomavirus-9 in 2011, MW polyomavirus and MX polyomaviruses in 2012, St Louis polyomavirus in 2013, New Jersey polyomavirus in 2014, and Lyon IARC polyomavirus in 2017.
Polyomaviruses are small (diameter 40 nm) non-enveloped viruses with a double-stranded DNA genome and an icosahedral capsid comprising three structural proteins, VP1, VP2, and VP3. The viral DNA is a supercoiled, circular, double-stranded DNA of approximately 5000 base pairs. The genome is organized into three regions (early, late, and regulatory), each of which has specific functions. ,
Polyomaviruses are ubiquitous, and several species-specific viruses exist, with infections observed in humans, monkeys, mice, cattle, rabbits, and birds. , Infection of human cells is generally limited to epithelial cells, fibroblasts, lymphocytes, or cells derived from the central nervous system. Polyomaviruses are important in human disease for two main reasons. First, although polyomavirus infections usually are asymptomatic, they can be associated with specific pathology. For example, BK virus infection can lead to polyomavirus-associated nephropathy, and JC virus infection can lead to progressive multifocal leukoencephalopathy (PML). Second, several polyomaviruses encode oncogenic proteins that can undergo transformation in cell cultures, have tumorigenic activity in animals, and might be associated with cancer in humans. ,
Epidemiology
The mode of transmission of polyomaviruses is not well known since clinical disease in immunocompetent individuals is rare. Primary infection mainly occurs in childhood and is largely asymptomatic or mildly symptomatic. Fecal–oral, oral, and respiratory routes of transmission have been suggested for different human polyomaviruses. Studies in urban sewage samples suggest that JC and BK viruses might be acquired through fecally-contaminated water, food, or fomites. , Salivary shedding suggests that the BK virus might be transmitted orally. KI and WU polyomaviruses also have been isolated from respiratory specimens of children and immunosuppressed adults, , , , and Merkel cell polyomavirus DNA can be detected in respiratory tract specimens of symptomatic individuals. , Transmission primarily occurs through close contact. However, other routes of transmission implicated for some polyomaviruses include blood transfusion, placenta, semen, and organ transplantation. ,
The prevalence of polyomaviruses varies by geography and age distribution. Seroprevalence rates for the human polyomaviruses in adults are 82%–99% for BK virus, 39%–81% for JC virus, 55%–90% for KI polyomavirus, 69%–98% for WU polyomavirus, 25%–81% for Merkel cell polyomavirus strains 350 and 339, and 70% for trichodysplasia spinulosa virus. Age-specific prevalence studies indicate that BK virus seroconversion peaks during childhood, and JC virus seroprevalence increases steadily from childhood into late adulthood. ,
Bk Virus
BK virus was isolated from the urine of a renal transplant recipient with ureteric stenosis, whose initials were BK. The virus is an important cause of morbidity in kidney transplant recipients, with a predilection to cause severe nephropathy in the allograft, leading to loss of the graft in up to 80% of patients. , BK virus also is associated with hemorrhagic cystitis in 25%–50% of patients with hematopoietic stem cell transplants. Other less commonly observed infections in immunocompromised hosts include pneumonitis, retinitis, liver disease, and meningoencephalitis.
Primary infection typically occurs in childhood and usually is asymptomatic or associated with mild upper respiratory symptoms. Primary infection is followed by dissemination of the virus to sites where it remains latent, predominantly the epithelial cells of collecting ducts, tubular epithelium of renal calyces, and renal pelvis. , BK viruria usually correlates with the degree of immunosuppression, but asymptomatic viruria has been described in healthy as well as immunocompromised patients. After renal or bone marrow transplantation, immunosuppression can lead to reactivation of the BK virus in host renal cells. Risk factors for reactivation include seropositivity, older age, and high pre-transplantation anti-BK virus immunoglobulin G.
Hematopoietic Stem Cell Transplant Recipients
Hemorrhagic cystitis usually is seen 2 weeks after transplantation, which is later than the hemorrhagic cystitis associated with cyclophosphamide. Symptoms include dysuria, urinary frequency and urgency, suprapubic pain, and hematuria. There is little difference between allogenic and autologous transplant recipients with respect to viruria. However, there is a higher incidence of hemorrhagic cystitis in allogeneic transplant patients with graft-versus-host disease, which is likely associated with immune reconstitution. Diagnosis is made by detection of BK virus DNA in the urine, but ideally should be confirmed with renal biopsy.
BK virus nephritis has been reported infrequently in hematopoietic stem cell transplant recipients and patients with leukemia. However, when it occurs, it can be severe and lead to permanent renal failure. Therefore, patients with unexplained deteriorating kidney function should be evaluated for BK virus infection by polymerase chain reaction analysis of urine and blood followed by renal biopsy for immunostaining. BK virus also can cause pneumonitis, hepatitis, retinitis, and meningoencephalitis in patients with cancer.
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