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Overview and virology of JC polyomavirus, BK polyomavirus, and other polyomavirus infections

Overview and virology of JC polyomavirus, BK polyomavirus, and other polyomavirus infections
Authors:
Hannah Imlay, MD, MS
Ajit P Limaye, MD, FACP, FIDSA
Section Editor:
Emily A Blumberg, MD
Deputy Editor:
Keri K Hall, MD, MS
Literature review current through: Jan 2024.
This topic last updated: Nov 03, 2022.

INTRODUCTION — Polyomaviruses have been detected in vertebrate hosts including rodents, cattle, birds, monkeys, and primates. Despite some common features with papillomaviruses, including an oncogenic potential in some species, polyomaviruses are recognized as members of the separate genus Polyomavirus in the Polyomaviridae family of the ungrouped DNA viruses.

An overview of the disease associations, clinical manifestations, diagnosis, virology, epidemiology, and pathogenesis of polyomavirus infections are provided here. Of the known human polyomaviruses (HPyVs), BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV) are the most studied and are associated with the established clinical diseases of BKPyV-associated nephropathy and progressive multifocal leukoencephalopathy, respectively. Merkel cell polyomavirus is the cause of Merkel cell carcinoma and discussed in detail elsewhere. Less is known about the remainder of the HPyVs.

●(See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

●(See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)

●(See "Progressive multifocal leukoencephalopathy (PML): Treatment and prognosis".)

●(See "Pathogenesis, clinical features, and diagnosis of Merkel cell (neuroendocrine) carcinoma".)

●(See "Staging, treatment, and surveillance of locoregional Merkel cell carcinoma".)

CLASSIFICATION

Human polyomaviruses — Human polyomaviruses (HPyVs) are members of a genus of DNA viruses in the Polyomaviridae family. Fourteen HPyV species have been identified (table 1).

Common clinically relevant species — BKPyV and JCPyV were first reported in the 1970s. BKPyV was isolated in tissue culture from the urine of a kidney transplant recipient with ureteral stenosis; JCPyV was isolated from the brain tissue of a patient with Hodgkin lymphoma and progressive multifocal leukoencephalopathy.

The remainder of the polyomaviruses were identified after 2000 using molecular techniques [1]. Merkel cell polyomavirus, isolated in 2008, is an oncogenic virus associated with Merkel cell carcinoma, an aggressive neuroendocrine malignancy of the skin. Trichodysplasia spinulosa polyomavirus, isolated in 2010, is associated with trichodysplasia spinulosa, characterized by the development of cutaneous keratin "spines" and follicular papules most commonly on the face. Definitive associations of other polyomaviruses with clinical disease are lacking. The absence of well-standardized serology, culture, or other detection methods have been obstacles to assessing prior infection and defining pathogenicity of many of the polyomaviruses [2].

Other viral species — The role of these HPyVs in human disease is less well established. Their known clinical manifestations and disease associations are discussed below. (See 'Clinical manifestations' below.)

Simian polyomavirus 40 — A simian polyomavirus virus (SV40) was discovered in 1960 as a contaminant of poliovirus and adenovirus vaccines and has been used as an experimental model of a DNA tumor virus and cell transformation. Despite human exposure to SV40 through contaminated attenuated poliovirus and adenovirus vaccines in the past, and possibly in wildlife reserves and animal facilities [3], serologic data do not support the independent circulation of SV40 in humans. Its possible role in human diseases including cancer has been controversial.

VIROLOGY

Structure and genome — Polyomavirus virions are small, nonenveloped icosahedral particles of 40 to 45 nm diameter that can endure heating to 50°C for 30 minutes with little effect on infectivity [1,4,5]. Polyomaviruses rely extensively on host cell machinery for replication, thereby limiting virus-specific antiviral targets [6]. Some genetic rearrangements may be correlated with pathogenicity [7-10].

Viral proteins — The small and large T antigens play a key role in the activation of polyomavirus replication in oncogenic transformation and host DNA instability. They are used as targets for various diagnostic assays (eg, nucleic acid amplification, immunohistochemistry). Similarly, the capsid VP-1 protein has been informative for defining polyomavirus serotypes, cellular immune recognition, neutralizing antibodies, and diagnostic antibody responses [7,11-18].

Receptor usage and cellular uptake — The polyomaviruses bind to different glycosylated receptors, which may be located on proteins or lipids, via the major capsid protein Vp1 [6]. Host cell receptors for BK polyomavirus, JCPyV, Merkel cell polyomavirus, and trichodysplasia spinulosa polyomavirus are specific and determine host cell tropism [6,19]. Specific binding and uptake mechanisms have been identified as targets for putative antivirals [6].

EPIDEMIOLOGY — Infections with the human polyomaviruses (HPyVs) are common, with seropositivity rates ranging from 30 to 90 percent, depending on the specific polyomavirus virus, in healthy adults [1]. The rates generally increase with increasing age and there are differences according to specific polyomavirus and geography.

Prevalence — The seroprevalence of infection with polyomaviruses rises with age. By adulthood, approximately 50 to 90 percent of adults have detectable antibodies to BKPyV, JCPyV, Merkel cell polyomavirus (MCPyV), Karolinska Institute polyomavirus (KIPyV), and Wisconsin University polyomavirus (WUPyV) [1,20-32]. The seroprevalence of trichodysplasia spinulosa polyomavirus (TSPyV) and MCPyV is at least 70 percent [1,6]; the seroprevalence of HPyV12, New Jersey polyomavirus, and LI polyomavirus is estimated to be ≤20 percent [33]. The timing of infection varies by age for each specific virus, suggesting that they circulate independently [34,35].

Transmission — Transmission occurs from person-to-person. No animal reservoir has been identified for BKPyV or JCPyV, though this has not been comprehensively studied for other HPyVs.

Specific transmission routes have not been definitively identified for any of the HPyVs and vary with the viral species. Oral and/or respiratory transmission has been strongly implicated for BKPyV, JCPyV, KIPyV, and WUPyV, whereas direct skin contact has been suggested for MCPyV, HPyV6, HPyV7, and TSPyV [20,36-40]. Other potential routes include fecal-oral [41-47], sexual routes [48,49], or perinatal transmission [50,51].

Geographic distribution — Among well-studied polyomaviruses (BKPyV, JCPyV, MCPyV), the geographic distribution of polyomavirus subtypes varies and may reflect migration patterns of the human population [7,21,52-58]. Differences among subtypes may impact serologic or molecular assays [21,59-61]; it is unknown whether subtypes are associated with varying pathogenicity or oncogenic potential [55].

PATHOGENESIS — The pathogenesis of human polyomaviruses (HPyVs) has been mostly studied in adults for JCPyV and BKPyV. Asymptomatic primary infection early in childhood is followed by lifelong persistence. Reactivated infection occurs occasionally in immunocompetent hosts, but in the setting of immunosuppression, reactivation and viral replication occur frequently and can occasionally progress to clinically recognized disease (See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis", section on 'Neuropathology' and "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Pathogenesis'.)

For BKPyV in kidney transplant recipients, as defined by detection of viral DNA by polymerase chain reaction, replication can be identified in urine (viruria) or in blood (viremia) and has been used to monitor progression of infection, to predict disease (BKPyV-associated nephropathy [BKPyVAN]) risk, and to monitor response to therapy. For BKPyV and JCPyV, virus-specific cellular (T cell) immune responses are correlated with risk for progressive infection, risk for developing clinical disease, and/or resolution of infection or disease [1,13,62-74].

Primary infection — Serologic evidence of infection is common, but little is known about the clinical manifestations of primary infection with these viruses. The majority of primary infections are either asymptomatic or cause a nonspecific viral syndrome [20,75].

During primary JCPyV and BKPyV infections of mucosal surfaces (eg, of the respiratory tract, oropharynx, and/or gastrointestinal tract), viremic spread occurs to other tissues and organs. For BKPyV and JCPyV, this includes the urinary tract as a principal site [76].

BKPyV and JCPyV are thought to persist after primary infection; clinical disease follows reactivation of prior infection in the setting of impaired host immunity [1,76]. Whether this is also true for other polyomaviruses has not been well established [1]. For trichodysplasia spinulosa polyomavirus (TSPyV), some evidence suggests that primary infection rather than reactivation could result in clinical disease. In one study, TSPyV-specific immunoglobulin (Ig)G responses were detected only after the onset of symptomatic trichodysplasia spinulosa, suggesting symptoms arose after primary TSPyV infection. However, another study found that TSPyV DNA was detectible in blood and urine two months prior to trichodysplasia spinulosa development in a kidney transplant recipient, supporting the paradigm that reactivation of TSPyV led to symptomatic trichodysplasia spinulosa [77-79].

Viruria — Following primary infection, detection of polyomavirus DNA in the urine is thought to represent active viral replication, which may occur at low levels in immunocompetent people. Higher levels of viruria are seen in immunocompromised hosts. Decoy cells found on urine cytology are a marker of high-level viruria caused by BKPyV or JCPyV corresponding to urine viral loads of more than 7 log10 copies/mL [80].

BKPyV and JCPyV urinary shedding is detectable in up to 10 to 30 percent of healthy blood donors at the time of blood donation, with median urine viral loads of 3500 (3.5 log10) copies/mL (BKPyV) and 50,000 (4.6 log10) copies/mL (JCPyV) [21,81,82]. The incidence of BKPyV or JCPyV viruria increases among immunosuppressed patients, including persons with HIV, systemic lupus erythematosus, pregnancy, or other forms of cellular immune deficiency; urine viral loads may increase to values higher than 7 log10 copies/mL, and “decoy cells” (urothelial or tubular epithelial cells with an enlarged nucleus and large basophilic intranuclear inclusions) may be detected by urine cytology [83-88].

This increase in urinary shedding is more pronounced for BKPyV than JCPyV in the setting of transplantation, particularly after kidney and hematopoietic cell transplantation [89-91], and it is usually asymptomatic. In solid organ transplant recipients other than kidney, viruria is seen in approximately 15 percent of patients, and median urine viral loads are typically lower than in kidney transplant recipients, at around 6 log10 copies/mL [92-99]. However, in the few cases of biopsy-confirmed BKPyV-associated nephropathy in native kidneys of nonrenal solid organ transplant recipients, similarly high urine and plasma BKPyV loads have been documented [92,99-101]. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

Viremia — In kidney recipients, the detection of BKPyV DNA in the blood has been found to be a marker of polyomavirus-associated nephropathy and the onset of renal disease is proportional to the grade of BKPyV viremia [5,6,89,102] and, in a prospective study, correlated with the onset and resolution of disease [89]. In transplant recipients other than kidneys, viremia with BKPyV or JCPyV is uncommon and usually of low level and without clinical significance [90,103]. In a study of 263 solid organ transplant recipients, viremia with BKPyV was observed in 26 percent of kidney transplant recipients and less frequently in heart (7 percent) or liver (4 percent) transplant recipients during the first year following transplantation [104]. Viremia with JCPyV was observed in 20 percent of kidney-pancreas transplant recipients, 8 percent of kidney transplant recipients, 7 percent of heart transplant recipients, and 2 percent of liver transplant recipients during the first year following transplantation. The majority of active infections were subclinical. In another study, renal or liver transplant recipients did not have any evidence of BK or JC viremia, although a significant proportion had asymptomatic viruria [90,92]. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

In persons with HIV without clinical disease, viremia with either BKPyV or JCPyV is uncommon [102,105,106]. JCPyV viremia can occur in up to 48 percent of patients with progressive multifocal leukoencephalopathy (PML) [103], but the correlation between JCPyV viruria and viremia with PML is inconsistent. (See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)

Viremia with most polyomaviruses is uncommon among healthy persons. Merkel cell polyomavirus (MCPyV) DNA was detected in 3.8 percent of healthy blood donors at time of donation but all other polyomaviruses had a rate of detection of <1 percent [107].

Onset of clinical disease — HPyV infection may result in different disease manifestations, which depend on whether or not there is sustained and/or high-level viral replication and the role of the associated host inflammatory response, which may mediate damage in some diseases [1,75,108-113]. Potential oncogenic effects of polyomaviruses are characterized by viral early gene expression activating host cells, but without subsequent late gene expression and cytopathic release of progeny virus. The prototype of this uncoupling is the genetic truncation of the MCPyV genome permitting viral small and large T antigen expression but not late viral gene expression due to chromosomal integration or mutations [114,115]. Uncoupling from capsid protein expression, assembly, and cell lysis may also underlie BKPyV-associated urothelial cancers [116]. The resulting oncogenic pathologies are not dependent on concurrent polyomavirus replication [115,117].

Host immune responses — In immunocompetent hosts, polyomavirus replication is controlled by limiting spread of progeny virus, especially hematogenous virion spread, through neutralizing antibodies and deleting replicating host cells by cytotoxic T cell responses. Host immune response to polyomaviruses have been most extensively studied for BKPyV and JCPyV.

There are several lines of evidence implicating the importance of cellular immunity in BKPyV- and JCPyV-associated infection and disease:

BKPyV:

●BKPyVAN and BKPyV-associated hemorrhagic cystitis (BKPyV-HC) are most frequently described among patients with cellular immune deficits rather than patients with isolated hypogammaglobulinemia [118-120].

●Increases in polyfunctional or BKPyV-specific T cells were associated with control of viremia following kidney transplant [13,24,62,63,121,122].

●Loss of BKPyV-specific T cells among kidney recipients pre- to post-transplant is correlated with increased risk of BKPyV replication post-transplant [65].

●Decrease of immunosuppression, the standard of care for treatment of BKPyVAN, was associated with a trend toward BKPyV-specific T cell recovery and resolution of BKPyV viremia in a portion of studied kidney recipients [68].

●CD4 and CD8 recovery is associated with BKPyV clearance in hematopoietic stem cell transplant patients with BKPyV-HC [123].

●The risk of BKPyV viruria and viremia in kidney transplantation has been linked to baseline levels of BKPyV-specific antibody titers in either donor or recipient [5,67,124-126]; however, it is possible that the presence or absence of BKPyV-specific antibody is a proxy for other (cellular) immune responses.

●Viral-specific T cells appear to be effective for some polyomavirus diseases [127,128].

JCPyV:

●PML nonsurvivors had impaired JCPyV-specific T cell responses versus T cell matched controls [71].

●The presence of JCPyV-specific cytotoxic T lymphocytes were associated with early control of PML [72].

●CD8+ cytotoxic T cells specific to JCPyV were found in PML survivors with HIV but not patients with progressive neurologic disease due to PML [70].

CLINICAL MANIFESTATIONS — Most instances of primary polyomavirus infection in immunocompetent persons are presumed to be either subclinical or associated with mild nonspecific symptoms. In immunocompromised persons, however, either primary infection and/or reactivated infection can cause specific syndromes and lead to substantial morbidity.

Human polyomavirus-associated diseases are more frequently encountered in specific patient populations, suggesting that the interaction of patient, organ, and virus determinants underlie the pathogenesis; the reasons for these associations are not fully understood [129].

Clinical syndromes that are causally linked with polyomavirus infection are best established for BKPyV, JCPyV, Merkel cell polyomavirus (MCPyV), and trichodysplasia spinulosa polyomavirus (TSPyV), and occur primarily in the setting of cellular immune deficiency.

BKPyV-associated nephropathy — BKPyV is the primary cause of polyomavirus-associated nephropathy in renal transplant recipients, which presents as progressive renal dysfunction resulting in either an asymptomatic acute or slowly progressive rise in serum creatinine and can progress to renal allograft loss. JCPyV is a rare cause of nephropathy in renal transplant recipients and may be due to primary infection. BKPyV-associated nephropathy in native kidneys is rare but has been described in nonkidney organ transplant recipients [96-101,130]. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

Hemorrhagic cystitis — Acute hemorrhagic cystitis following engraftment among hematopoietic cell transplant (HCT) recipients (particularly allogeneic HCT recipients) may be associated with BKPyV infection. (See "Overview of infections following hematopoietic cell transplantation", section on 'Hemorrhagic cystitis'.)

BKPyV-associated hemorrhagic cystitis (BKPyV-HC) is estimated to complicate 5 to 25 percent of allogeneic HCT and is typically characterized by postengraftment urinary frequency, dysuria, hematuria, urinary blood clots, and urinary obstruction that may last for several weeks [131-136].

BKPyV viruria is common post-transplant, affecting >50 percent of HCT recipients [137-140]. However, most patients with viruria do not develop symptomatic diseases. The likelihood of developing symptoms and disease severity appear to correlate with the degree of viruria and viremia [131,133,136,137,141-146]. Other causes of hemorrhagic cystitis that should be considered in HCT recipients include cyclophosphamide toxicity, adenovirus, and bacterial infection.

There are at least two major hypotheses for the pathogenesis of BKPyV-HC. The first is a multistep process that involves both viral and immune-mediated urothelial damage: (1) conditioning regimens damage urothelial mucosa, (2) BKPyV reactivates and replicates during host immune suppression, and (3) donor immune cells attack viral antigens, which perpetuates bladder and mucosal damage [108,133,147]. The second hypothesis involves BKPyV-induced cytopathic effects on bladder cells following chemotherapy-induced injury without an explicit role of immune-mediated mechanisms [141].

The cornerstone of treatment for BKPyV-HC is supportive care. Although both intravesicular and intravenous cidofovir have been used in patients with BKPyV-HC [148], there have been no controlled trials to evaluate the possible benefit of either approach and some observational studies suggest lack of benefit [131,146,149]. Some studies have suggested potential benefit of BKPyV-specific cytotoxic T cell therapy [127,128,146,150,151].  

Progressive multifocal leukoencephalopathy — JCPyV is the main causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disorder that almost always occurs in the setting of immunocompromise, and presents with progressive focal neurologic deficits including ataxia, hemiparesis, visual field deficits, and cognitive impairment. PML has been reported most commonly in patients with advanced HIV (particularly before the availability of potent antiretroviral therapy), but it has also been reported in patients with hematologic malignancies and in patients receiving certain lymphocyte-targeted agents, such as natalizumab.

●(See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis", section on 'Epidemiology'.)

●(See "Clinical use of monoclonal antibody disease-modifying therapies for multiple sclerosis", section on 'Natalizumab'.)

●(See "Progressive multifocal leukoencephalopathy (PML): Treatment and prognosis".)

Trichodysplasia spinulosa — Trichodysplasia spinulosa (TS) polyomavirus (TSPyV) has been detected in lesions of TS, a rare skin disease in immunocompromised patients characterized by viral replication within keratinocytes and hyperproliferation of the inner root sheath cell (picture 1) [78,79,152-155]. The diagnosis is characterized by the development of keratin spines (“spicules”) and follicular papules that often involve the face [6,153,156] and is confirmed by a skin biopsy with characteristic histology or detection of the polyomavirus (SV-40 immunostaining, electron microscopy visualization of 40 to 45 nm viral particles in cells of the inner root sheath or molecular methods) [79,157]. In addition to improving immune function (eg, by reducing immunosuppression), case reports have described improvement following topical cidofovir, valganciclovir, leflunomide, retinoids, or physical extraction of keratin spicules [152,157], but controlled trials are lacking [6].

Associations with malignancy

Merkel cell carcinoma — MCPyV DNA or virions are commonly found on healthy skin [158]. Although rare, the virus is implicated in the pathogenesis of Merkel cell carcinoma, an aggressive neuroendocrine malignancy that affects the skin. Multiple independent clonal integration sites and the presence of functionally truncating alterations of the viral genome support its etiologic role [115,117]. (See "Pathogenesis, clinical features, and diagnosis of Merkel cell (neuroendocrine) carcinoma", section on 'Merkel cell polyomavirus'.)

Putative associations — JCPyV and BKPyV have been associated with an array of malignancies but whether they play a causal role is uncertain [159,160]. Viral DNA sequences and viral protein expression has been detected in some tumor involving the brain, prostate, bladder, urothelium, and other organs. There is also a higher than expected incidence of bladder cancer in kidney transplant recipients treated for BKPyV-associated nephropathy [161-165].

Other disease associations — Numerous other diseases have been associated with polyomaviruses, however, the causal role for the association is not well established.

●Disseminated BKPyV infection − Case reports have suggested rare multiorgan infection with BKPyV with histology and/or immunohistochemistry confirming systemic spread of BKPyV to kidneys, lungs, brain, bladder, gastrointestinal tract, cardiac, and endothelial cells [166-175]. Systemic spread may be linked to rearrangements in noncoding regions [9,168,175]. Examples include:

•Widespread endothelial BKPyV infection in a kidney transplant recipient resulted in severe muscle weakness, anasarca, and a fatal myocardial infarction [166]. At autopsy, endothelial cells in the heart, skeletal muscles, and esophagus showed transformed nuclei, nuclear inclusions, and apoptosis; polymerase chain reaction testing of kidney, muscle, and heart tissues was positive for BKPyV. Molecular analysis and experimental testing suggested a more virulent BKPyV variant due to constitutive early viral gene expression; the noncoding region was unable to be amplified suggestive of additional mutations in this area.

•BKPyV viremia, dysuria, and hematuria in a postallogeneic stem cell transplant recipient progressed to deterioration of renal function, hypertension, seizure, pancreatitis, and respiratory failure. Histologic examination revealed evidence of BKPyV infection in lungs, pancreas, and kidneys at autopsy [175]. Sequencing revealed major rearrangements in the noncoding BKPyV-noncoding control region domain that regulates viral replication.  

•Colonic ulcers were documented in a kidney transplant recipient with abdominal pain and known BKPyV infection of the kidney allograft with associated BK viremia [167]. Biopsy specimens of the ulcers showed viral inclusion bodies, and in situ hybridization for BKPyV was strongly positive. Reduction in the immunosuppressive regimen led to healing of the ulcers and a decrease in serum BKPyV DNA. Studies for other viruses, including cytomegalovirus, were negative.

●Trichodysplasia spinulosa polyoma virus (TSPyV) has also been found in respiratory samples of a child with acute lymphoblastic leukemia who had cough, fever, and coryza [176]. TSPyV has been found in blood and urine samples of otherwise asymptomatic transplant recipients [79].

●Karolinska Institute polyomavirus (KIPyV) has been detected in respiratory and fecal specimens in immune competent pediatric patients but its role in respiratory tract disease remains uncertain [1,177-180].

●Wisconsin University polyomavirus (WUPyV) was initially detected in respiratory specimens among immune competent patients with respiratory tract infection and has now also been identified in blood, urine, and feces. There is a single report of detection in cerebrospinal fluid (CSF) by polymerase chain reaction in a retrospective analysis of CSF samples from patients with suspected viral encephalitis, in a patient with HIV/AIDS and brain magnetic resonance imaging findings consistent with progressive multifocal leukoencephalopathy. Although hypothesized to cause acute respiratory infection, no putative disease associations have been confirmed [1,2,177-182].

●Human polyomavirus 6 (HPyV6) has been reported in association with pruritic, hyperpigmented skin eruptions in two patients, one with a history of kidney and pancreas transplant and the other with no history of immune compromise [183] but a causal role of HPyV6 has not been definitively established. HPyV6 has also been detected in normal skin, feces, and in the nasopharynx of asymptomatic healthy persons and in urine of asymptomatic persons with systemic lupus erythematosus, pregnancy, and HIV [1,152,158,184,185].

●Human polyomavirus 7 (HPyV7) has been associated with a pruritic rash and viremia in two lung transplant recipients, a heart transplant recipient, and in a patient with HIV/AIDS. It has also been detected in normal skin, nasopharynx, and urine of asymptomatic persons [1,152,158,183-186].

●Human polyomavirus 9 (HPyV9) has been detected in several immunocompromised patients (ie, transplant recipients, patients with HIV) in a study performed for other purposes [187,188]. HPyV9 has also been detected in plasma, respiratory, and urine samples of asymptomatic pregnant and non-pregnant women [1,184,189].

●Human polyomavirus 10 (HPyV10) has been detected in stool samples of children with diarrhea and in normal feces [45,184]. HPyV10 also has been isolated from anal condylomata in a single patient with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome [190].

●Human polyomavirus 11 and 12 (HPyV11 and HPyV12) have been found in stool samples of immune competent children with and without diarrhea. HPyV12 was originally detected in liver tissue of a deceased organ donor as part of large-scale molecular virus screening [45,184,191].

●Human polyomavirus 13 (HPyV13) has been detected in a muscle biopsy from a single pancreas recipient with vasculitis, myositis, and retinal blindness [192].

●Human polyomavirus 14 (HPyV14) has been isolated from skin swabs, eyebrow hairs, and oral gargles in a longitudinal study of human papillomaviruses in healthy adults [193].

SUMMARY

●Human polyomaviruses (HPyVs) are members of a genus of DNA viruses in the Polyomaviridae family. The most common polyomaviruses associated with infectious diseases are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV). Other polyomaviruses include Merkel cell polyomavirus (MCPyV), as well as trichodysplasia spinulosa polyomavirus (TSPyV), Karolinska Institute polyomavirus (KIPyV), and Wisconsin University polyomavirus (WUPyV).

●Polyomavirus virions are small, nonenveloped icosahedral particles of 40 to 45 nm diameter that can survive heating to 50°C for 30 minutes with little effect on infectivity. The circular double-stranded DNA genome of approximately 5000 base pairs can be divided into three parts: the noncoding control region, the early viral gene region, and the late viral gene region. (See 'Virology' above.)

●Serologic evidence of infection with JCPyV and BKPyV as well as of other HPyVs is widespread, but significant clinical manifestations are rare in immunocompetent hosts. The major clinical manifestations appear to result from reactivation and high-level replication in persons with significant cellular immune deficits. (See 'Clinical manifestations' above.)

●In immunocompromised hosts, JCPyV infection can lead to progressive multifocal leukoencephalopathy (PML), a demyelinating disease of high morbidity and mortality. PML has been reported most commonly in patients with advanced HIV infection (particularly before the availability of potent antiretroviral therapy), but it has also been reported in patients with hematologic malignancies and in patients receiving certain immunosuppressive agents, such as natalizumab. (See 'Progressive multifocal leukoencephalopathy' above and "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)

●BKPyV can cause nephropathy in kidney transplant recipients and hemorrhagic cystitis in hematopoietic cell transplantation recipients. (See 'BKPyV-associated nephropathy' above and 'Hemorrhagic cystitis' above.)

●Several other polyomaviruses have been observed less commonly than JCPyV and BKPyV:

•MCPyV infection has been associated with Merkel cell carcinoma. (See 'Merkel cell carcinoma' above and "Pathogenesis, clinical features, and diagnosis of Merkel cell (neuroendocrine) carcinoma".)

•TSPyV has been associated with trichodysplasia spinulosa, a rare skin disease characterized by spiculae and alopecia in immunocompromised patients. (See 'Trichodysplasia spinulosa' above.)

●Several other HPyVs have been associated with human disease. However, whether they play a causal role is unclear. (See 'Other disease associations' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Lisa M Demeter, MD, and Hans H Hirsch, MD, MSc, who contributed to an earlier version of this topic review.

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  167. Kim GY, Peji J, Nuovo G, Thomas F. BK virus colonic ulcerations. Clin Gastroenterol Hepatol 2004; 2:175.
  168. Stoner GL, Alappan R, Jobes DV, et al. BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a leukemia patient with tubulointerstitial nephritis and meningoencephalitis. Am J Kidney Dis 2002; 39:1102.
  169. Akazawa Y, Terada Y, Yamane T, et al. Fatal BK virus pneumonia following stem cell transplantation. Transpl Infect Dis 2012; 14:E142.
  170. Lee Y, Kim YJ, Cho H. BK virus nephropathy and multiorgan involvement in a child with heart transplantation
. Clin Nephrol 2019; 91:107.
  171. Sandler ES, Aquino VM, Goss-Shohet E, et al. BK papova virus pneumonia following hematopoietic stem cell transplantation. Bone Marrow Transplant 1997; 20:163.
  172. Bratt G, Hammarin AL, Grandien M, et al. BK virus as the cause of meningoencephalitis, retinitis and nephritis in a patient with AIDS. AIDS 1999; 13:1071.
  173. Cubukcu-Dimopulo O, Greco A, Kumar A, et al. BK virus infection in AIDS. Am J Surg Pathol 2000; 24:145.
  174. Vallbracht A, Löhler J, Gossmann J, et al. Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease. Am J Pathol 1993; 143:29.
  175. Roy S, Mieczkowski PA, Weida C, et al. BK polyomavirus nephropathy with systemic viral spread: Whole genome sequencing data from a fatal case of BKPyV infection. Transpl Infect Dis 2020; 22:e13269.
  176. Bagasi AA, Khandaker T, Clark G, et al. Trichodysplasia Spinulosa Polyomavirus in Respiratory Tract of Immunocompromised Child. Emerg Infect Dis 2018; 24:1744.
  177. Venter M, Visser A, Lassauniere R. Human polyomaviruses, WU and KI in HIV exposed children with acute lower respiratory tract infections in hospitals in South Africa. J Clin Virol 2009; 44:230.
  178. Mourez T, Bergeron A, Ribaud P, et al. Polyomaviruses KI and WU in immunocompromised patients with respiratory disease. Emerg Infect Dis 2009; 15:107.
  179. Huijskens EG, van Erkel AJ, Peeters MF, Rossen JW. Human polyomavirus KI and WU in adults with community acquired pneumonia in The Netherlands, 2008-2009. J Clin Virol 2010; 49:306.
  180. Kuypers J, Campbell AP, Guthrie KA, et al. WU and KI polyomaviruses in respiratory samples from allogeneic hematopoietic cell transplant recipients. Emerg Infect Dis 2012; 18:1580.
  181. Barzon L, Squarzon L, Pacenti M, et al. Detection of WU polyomavirus in cerebrospinal fluid specimen from a patient with AIDS and suspected progressive multifocal leukoencephalopathy. J Infect Dis 2009; 200:314.
  182. Babakir-Mina M, Ciccozzi M, Perno CF, Ciotti M. The novel KI, WU, MC polyomaviruses: possible human pathogens? New Microbiol 2011; 34:1.
  183. Nguyen KD, Lee EE, Yue Y, et al. Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses. J Am Acad Dermatol 2017; 76:932.
  184. Ehlers B, Wieland U. The novel human polyomaviruses HPyV6, 7, 9 and beyond. APMIS 2013; 121:783.
  185. Prezioso C, Van Ghelue M, Moens U, Pietropaolo V. HPyV6 and HPyV7 in urine from immunocompromised patients. Virol J 2021; 18:24.
  186. Ho J, Jedrych JJ, Feng H, et al. Human polyomavirus 7-associated pruritic rash and viremia in transplant recipients. J Infect Dis 2015; 211:1560.
  187. van der Meijden E, Wunderink HF, van der Blij-de Brouwer CS, et al. Human polyomavirus 9 infection in kidney transplant patients. Emerg Infect Dis 2014; 20:991.
  188. Wang Y, Strassl R, Helanterä I, et al. Multiplex analysis of Human Polyomavirus diversity in kidney transplant recipients with BK virus replication. J Clin Virol 2019; 120:6.
  189. Scuda N, Hofmann J, Calvignac-Spencer S, et al. A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus. J Virol 2011; 85:4586.
  190. Buck CB, Phan GQ, Raiji MT, et al. Complete genome sequence of a tenth human polyomavirus. J Virol 2012; 86:10887.
  191. Korup S, Rietscher J, Calvignac-Spencer S, et al. Identification of a novel human polyomavirus in organs of the gastrointestinal tract. PLoS One 2013; 8:e58021.
  192. Mishra N, Pereira M, Rhodes RH, et al. Identification of a novel polyomavirus in a pancreatic transplant recipient with retinal blindness and vasculitic myopathy. J Infect Dis 2014; 210:1595.
  193. Gheit T, Dutta S, Oliver J, et al. Isolation and characterization of a novel putative human polyomavirus. Virology 2017; 506:45.
Topic 8280 Version 14.0

References

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7 : Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology.

8 : Rearranged JC virus noncoding control regions found in progressive multifocal leukoencephalopathy patient samples increase virus early gene expression and replication rate.

9 : Sp1 sites in the noncoding control region of BK polyomavirus are key regulators of bidirectional viral early and late gene expression.

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11 : Polyoma virus infection is a prominent risk factor for bladder carcinoma in immunocompetent individuals.

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13 : Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients.

14 : Genotyping schemes for polyomavirus BK, using gene-specific phylogenetic trees and single nucleotide polymorphism analysis.

15 : Biologic diversity of polyomavirus BK genomic sequences: Implications for molecular diagnostic laboratories.

16 : Antibody responses to recombinant polyomavirus BK large T and VP1 proteins in young kidney transplant patients.

17 : Polyomavirus BK-specific immunity after kidney transplantation.

18 : Cellular immune responses to BK virus.

19 : Virus receptors and tropism.

20 : Serological evidence of Merkel cell polyomavirus primary infections in childhood.

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

22 : Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC virus (JCV).

23 : Quantitation of human seroresponsiveness to Merkel cell polyomavirus.

24 : BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication.

25 : Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40.

26 : High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland.

27 : Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma.

28 : The human JC polyomavirus (JCPyV): virological background and clinical implications.

29 : Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.

30 : High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors.

31 : Serologic evidence of frequent human infection with WU and KI polyomaviruses.

32 : Seroepidemiology of human polyomaviruses.

33 : Effect of the Large and Small T-Antigens of Human Polyomaviruses on Signaling Pathways.

34 : Age-specific seroprevalences of merkel cell polyomavirus, human polyomaviruses 6, 7, and 9, and trichodysplasia spinulosa-associated polyomavirus.

35 : Seroprevalence of human Malawi polyomavirus.

36 : The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils.

37 : Identification of the novel KI and WU polyomaviruses in human tonsils.

38 : Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: implications for respiratory transmission and latency.

39 : Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection.

40 : Merkel cell polyomavirus DNA in persons without merkel cell carcinoma.

41 : Polyomavirus shedding in the stool of healthy adults.

42 : Excretion of the novel polyomaviruses KI and WU in the stool of patients with hematological disorders.

43 : Frequent detection of polyomaviruses in stool samples from hospitalized children.

44 : High frequency of polyoma BK virus shedding in the gastrointestinal tract after hematopoietic stem cell transplantation: a prospective and quantitative analysis.

45 : Human polyomaviruses 10 and 11 in faecal samples from Brazilian children.

46 : Documenting the epidemiologic patterns of polyomaviruses in human populations by studying their presence in urban sewage.

47 : Potential transmission of human polyomaviruses through the gastrointestinal tract after exposure to virions or viral DNA.

48 : Latent BK virus infection and Kaposi's sarcoma pathogenesis.

49 : Association between the JC polyomavirus infection and male infertility.

50 : Occurrence of IgM antibodies against BK and JC polyomaviruses during pregnancy.

51 : BK virus sequences in specimens from aborted fetuses.

52 : Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in American, European and Asian populations suggest co-migration of BKV and the human race.

53 : Source and Relevance of the BK Polyomavirus Genotype for Infection After Kidney Transplantation.

54 : Evolution of human Polyomavirus JC: implications for the population history of humans.

55 : Evolution and molecular epidemiology of polyomaviruses.

56 : DNA sequencing of viral capsid protein VP-1 region in patients with BK virus interstitial nephritis.

57 : Molecular genetics of the BK virus.

58 : Evolution of the BK polyomavirus: epidemiological, anthropological and clinical implications.

59 : Identification of species-specific and cross-reactive epitopes in human polyomavirus capsids using monoclonal antibodies.

60 : Identification of species-specific and cross-reactive epitopes in human polyomavirus capsids using monoclonal antibodies.

61 : BK polyomavirus genotypes in renal transplant recipients in the United States: A meta-analysis.

62 : Increased Frequency of BK Virus-Specific Polyfunctional CD8+ T Cells Predict Successful Control of BK Viremia After Kidney Transplantation.

63 : Quantitative analysis of BKV-specific CD4+ T cells before and after kidney transplantation.

64 : Antigen-Specificity of T Cell Infiltrates in Biopsies With T Cell-Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing.

65 : The Loss of BKV-specific Immunity From Pretransplantation to Posttransplantation Identifies Kidney Transplant Recipients at Increased Risk of BKV Replication.

66 : The role of CD4(+) T cells in BKV-specific T cell immunity.

67 : BK polyomavirus-specific antibody and T-cell responses in kidney transplantation: update.

68 : BK Polyomavirus-specific T cell immune responses in kidney transplant recipients diagnosed with BK Polyomavirus-associated nephropathy.

69 : The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response.

70 : JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy.

71 : JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.

72 : A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathy.

73 : CD8 T Cells and STAT1 Signaling Are Essential Codeterminants in Protection from Polyomavirus Encephalopathy.

74 : Lack of specific T- and B-cell clonal expansions in multiple sclerosis patients with progressive multifocal leukoencephalopathy.

75 : Polyomavirus BK.

76 : Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues.

77 : Viremia and viruria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient.

78 : Primary Polyomavirus Infection, Not Reactivation, as the Cause of Trichodysplasia Spinulosa in Immunocompromised Patients.

79 : Recent developments in trichodysplasia spinulosa disease.

80 : Polyomavirus BK versus JC replication and nephropathy in renal transplant recipients: a prospective evaluation.

81 : Prevalence and patterns of polyomavirus urinary excretion in immunocompetent adults and children.

82 : Persistent JC virus (JCV) infection is demonstrated by continuous shedding of the same JCV strains.

83 : Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects.

84 : Prevalence of long-term BK and JC excretion in HIV-infected adults and lack of correlation with serological markers.

85 : 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.

86 : A prospective study of human polyomavirus infection in pregnancy.

87 : Dynamics of pregnancy-associated polyomavirus urinary excretion: a prospective longitudinal study.

88 : Novel human polyomaviruses in pregnancy: higher prevalence of BKPyV, but no WUPyV, KIPyV and HPyV9.

89 : Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients.

90 : A comparative study of BK and JC virus infections in organ transplant recipients.

91 : BK and JC virus infections in recipients of bone marrow transplants.

92 : Renal failure five years after lung transplantation due to polyomavirus BK-associated nephropathy.

93 : Polyomavirus BK non-coding control region rearrangements in health and disease.

94 : Prevalence of BK virus replication among recipients of solid organ transplants.

95 : Polyomavirus infection and its impact on renal function and long-term outcomes after lung transplantation.

96 : A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction.

97 : Prospective monitoring of BK polyomavirus infection early posttransplantation in nonrenal solid organ transplant recipients.

98 : A prospective longitudinal study of polyomavirus shedding in lung-transplant recipients.

99 : BK virus-associated nephropathy in a lung transplant patient: case report and literature review.

100 : BK virus nephropathy without haemorrhagic cystitis following bone marrow transplantation.

101 : BK Nephropathy as a Cause of Renal Dysfunction in an ABO-incompatible Liver Transplant Patient.

102 : Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy.

103 : Diagnostic and Prognostic Value of JC Virus DNA in Plasma in Progressive Multifocal Leukoencephalopathy.

104 : A longitudinal molecular surveillance study of human polyomavirus viremia in heart, kidney, liver, and pancreas transplant patients.

105 : HIV-1-infected patients with focal neurologic signs: diagnostic role of PCR for Toxoplasma gondii, Epstein-Barr virus, and JC virus.

106 : JC virus antibody and viremia as predictors of progressive multifocal leukoencephalopathy in human immunodeficiency virus-1-infected individuals.

107 : Prevalence of DNA of fourteen human polyomaviruses determined in blood donors.

108 : BK virus: opportunity makes a pathogen.

109 : Polyomavirus infections in transplant recipients

110 : Immune reconstitution in HIV-infected patients.

111 : Fatal immune restoration disease in human immunodeficiency virus type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution.

112 : Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring.

113 : Molecular evaluation of BK polyomavirus nephropathy.

114 : Clonal integration of a polyomavirus in human Merkel cell carcinoma.

115 : Merkel cell carcinoma: An update and review: Pathogenesis, diagnosis, and staging.

116 : Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent.

117 : Merkel cell carcinoma: An update and review: Current and future therapy.

118 : Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation.

119 : BK Polyomavirus-Biology, Genomic Variation and Diagnosis.

120 : Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients.

121 : Reduced Risk of BK Polyomavirus Infection in HLA-B51-positive Kidney Transplant Recipients.

122 : BK Polyomavirus-specific T Cells as a Diagnostic and Prognostic Marker for BK Polyomavirus Infections After Pediatric Kidney Transplantation.

123 : Viral-specific T-cell response in hemorrhagic cystitis after haploidentical donor stem cell transplantation.

124 : BK virus antibody titers and intensity of infections after renal transplantation.

125 : Pretransplantation Donor-Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation.

126 : Correlation of BK Virus Neutralizing Serostatus With the Incidence of BK Viremia in Kidney Transplant Recipients.

127 : Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT.

128 : Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.

129 : Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.

130 : Native kidney BK virus nephropathy, a systematic review.

131 : Presentation of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

132 : BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis.

133 : ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients.

134 : Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation.

135 : Viral-induced Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplant.

136 : High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

137 : Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation.

138 : BK virus infection is associated with hematuria and renal impairment in recipients of allogeneic hematopoetic stem cell transplants.

139 : Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

140 : The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality.

141 : BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients.

142 : Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.

143 : Polyomavirus BK infection in blood and marrow transplant recipients.

144 : BK Viremia as a Predictor of Hemorrhagic Cystitis in Adults During the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation.

145 : Blood, and not urine, BK viral load predicts renal outcome in children with hemorrhagic cystitis following hematopoietic stem cell transplantation.

146 : The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation.

147 : The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation.

148 : Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

149 : Severe hemorrhagic cystitis caused by the BK polyomavirus is associated with decreased survival post-allogeneic hematopoietic stem cell transplantation.

150 : BK virus-specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation.

151 : BKV-specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA-haploidentical haematopoietic cell transplantation.

152 : Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses.

153 : Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient.

154 : Viral-associated trichodysplasia in a patient with lymphoma: a case report and review.

155 : Trichodysplasia spinulosa: a comprehensive review of the disease and its treatment.

156 : Trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host.

157 : Pediatric trichodysplasia spinulosa: A report of 2 cases and review of the literature.

158 : Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin.

159 : Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin.

160 : Human polyomaviruses in disease and cancer.

161 : BK virus and human cancer: innocent until proven guilty.

162 : Detection and expression of human BK virus sequences in neoplastic prostate tissues.

163 : Novel human polyomaviruses--re-emergence of a well known virus family as possible human carcinogens.

164 : Prospective study of JC virus seroreactivity and the development of colorectal cancers and adenomas.

165 : Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States.

166 : BK-related polyomavirus vasculopathy in a renal-transplant recipient.

167 : BK virus colonic ulcerations.

168 : BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a leukemia patient with tubulointerstitial nephritis and meningoencephalitis.

169 : Fatal BK virus pneumonia following stem cell transplantation.

170 : BK virus nephropathy and multiorgan involvement in a child with heart transplantation
.

171 : BK papova virus pneumonia following hematopoietic stem cell transplantation.

172 : BK virus as the cause of meningoencephalitis, retinitis and nephritis in a patient with AIDS.

173 : BK virus infection in AIDS.

174 : Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease.

175 : BK polyomavirus nephropathy with systemic viral spread: Whole genome sequencing data from a fatal case of BKPyV infection.

176 : Trichodysplasia Spinulosa Polyomavirus in Respiratory Tract of Immunocompromised Child.

177 : Human polyomaviruses, WU and KI in HIV exposed children with acute lower respiratory tract infections in hospitals in South Africa.

178 : Polyomaviruses KI and WU in immunocompromised patients with respiratory disease.

179 : Human polyomavirus KI and WU in adults with community acquired pneumonia in The Netherlands, 2008-2009.

180 : WU and KI polyomaviruses in respiratory samples from allogeneic hematopoietic cell transplant recipients.

181 : Detection of WU polyomavirus in cerebrospinal fluid specimen from a patient with AIDS and suspected progressive multifocal leukoencephalopathy.

182 : The novel KI, WU, MC polyomaviruses: possible human pathogens?

183 : Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses.

184 : The novel human polyomaviruses HPyV6, 7, 9 and beyond.

185 : HPyV6 and HPyV7 in urine from immunocompromised patients.

186 : Human polyomavirus 7-associated pruritic rash and viremia in transplant recipients.

187 : Human polyomavirus 9 infection in kidney transplant patients.

188 : Multiplex analysis of Human Polyomavirus diversity in kidney transplant recipients with BK virus replication.

189 : A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus.

190 : Complete genome sequence of a tenth human polyomavirus.

191 : Identification of a novel human polyomavirus in organs of the gastrointestinal tract.

192 : Identification of a novel polyomavirus in a pancreatic transplant recipient with retinal blindness and vasculitic myopathy.

193 : Isolation and characterization of a novel putative human polyomavirus.

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