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Polyomaviruses are ancient DNA viruses that infect several species of animals. While recognition of the family Polyomaviridae has grown rapidly, there are few studies that consider their potential association with disease. Carnivora are a diverse and widespread order affected by polyomaviruses (PyVs) that have co-evolved with their hosts for millions of years. PyVs have been identified in sea lions, raccoons, badgers, Weddell seals, and dogs. We have discovered a polyomavirus, tentatively named "Ursus americanus polyomavirus 1" (UaPyV1) in black bears (Ursus americanus). UaPyV1 was detectable in various tissues of six out of seven bears submitted for necropsy. Based on viral phylogenetic clustering and detection of the virus in multiple individuals, we suggest that black bears are the natural hosts for UaPyV1. In this albeit small group, there is no clear relationship between UaPyV1 infection and any specific disease.

Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55 697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N = 48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval [CI] 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9-5.4; N = 89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa-associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study., Methods: Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction., Results: MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03-4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01-6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively., Conclusion: MCPyV infection is highly prevalent in adults, with age and race being predisposing factors., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In 1960, J. Anthony Morris, a molecular biologist at the US National Institutes of Health conducted one of the only non-therapeutic clinical studies of the cancer virus SV40. Morris and his research team aimed to determine whether SV40 was a serious harm to human health, since many scientists at the time suspected that SV40 caused cancer in humans based on evidence from in vivo animal studies and experiments with human tissue. Morris found that SV40 had no significant effect but his claim has remained controversial among scientists and policymakers through the present day--both on scientific and ethical grounds. Why did Morris only conduct one clinical study on the cancer-causing potential of SV40 in healthy humans? We use the case to explain how empirical evidence and ethical imperatives are, paradoxically, often dependent on each other and mutually exclusive in clinical research, which leaves answers to scientific and ethical questions unsettled. This paper serves two goals: first, it documents a unique--and uniquely important--study of clinical research on SV40. Second, it introduces the concept of "the stowaway," which is a special type of contaminant that changes the past in the present moment. In the history of science, stowaways are misfortunes that nonetheless afford research that otherwise would have been impossible specifically by creating new pasts. This case (Morris' study) and concept (the stowaway) bring together history of science and philosophy of history for productive dialog., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Objectives: BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia., Design, Setting, Participants, & Measurements: Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months., Results: At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period., Conclusions: A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

The family Polyomaviridae is comprised of circular double-stranded DNA viruses, several of which are associated with diseases, including cancer, in immunocompromised patients. Here we describe a novel polyomavirus recovered from the fecal microbiota of a child in Malawi, provisionally named STL polyomavirus (STLPyV). We detected STLPyV in clinical stool specimens from USA and The Gambia at up to 1% frequency. Complete genome comparisons of two STLPyV strains demonstrated 5.2% nucleotide divergence. Alternative splicing of the STLPyV early region yielded a unique form of T antigen, which we named 229T, in addition to the expected large and small T antigens. STLPyV has a mosaic genome and shares an ancestral recombinant origin with MWPyV. The discovery of STLPyV highlights a novel alternative splicing strategy and advances our understanding of the complex evolutionary history of polyomaviruses., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types.

Background: Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV) and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases., Findings: We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT) gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST) gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350., Conclusions: This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.

Background: Infection of BK or JC human polyomavirus can lead to polyomavirus-associated nephropathy in renal transplant patients. Thus effective management of these patients requires early detection and quantification of these viruses in urine and blood., Design: The aim of this study was to evaluate and validate a multiplex real-time PCR-based method for monitoring BK and/or JC viral loads in renal transplant patients. Analytic parameters such as limit of quantification, linear dynamic range, sensitivity and specificity, as well as reliability of the assays were determined. Seventy-six plasma or urine samples spiked with variable amounts of BK and JC viral DNA ranging from low (7.0 x 10(3) or 1.5 x 10(4)), to medium (1.0 x 10(6) to high (1.0 x 10(8) or 1.0109 copies/mL) levels of viruses were tested. In addition, 45 clinical urine or plasma samples with known copy numbers of BK or JC viruses, which were isolated from the renal transplant patients from 4 US medical centers, were also tested., Results: BK and/or JC viruses can be detected with distinguishable melting temperature of 64 degrees C or 68 degrees C, respectively. On the basis of the need for clinical monitoring of different types of specimens, the low limit of quantification for plasma or urine was set at 7.0 x 10(3) or 1.5 x 10(4) copies/mL, respectively with the linear dynamic range Z6 logs. The assay exhibits 100% specificity, 97.9% sensitivity with low intra-assay and interassay variability (coefficient of variation <4%)., Conclusions: This clinically validated method has the necessary utility to monitor BK and JC viremia and viruria in renal transplant patients.

Background: Asbestos exposure is the only cause of epidemiological relevance for pleural malignant mesothelioma (MM), but the mechanism of action is not entirely understood. A causal role was suggested for SV40 since viral DNA and proteins were detected in pleural MM and SV40 caused MM in hamsters. SV40 proteins (Tag) interact with oncogenes P53 and Rb., Objectives: To review evidence on the association of SV40 with MM, bearing in mind laboratory and epidemiological studies., Methods: The review on SV40 was based on scientific papers published since 1990 on association of SV40 with human cancer., Results: Studies researching SV40 DNA in MM tissue observed a wide range of prevalences (0% to 70%); causes of variability were not convincingly identified. An association of MM with SV40 was suggested but confounding factors and biases were not considered. Cohort studies on humans inoculated with contaminated vaccines did not show an increased incidence but their statistical power was limited. Diffusion of SV40 in humans is linked to polio vaccines produced in 1955-63 from SV40-infected monkeys. A 11-12% prevalence of SV40 in adults were reported in the USA, 2-6% in Europe and Africa. The age pattern of MM does not suggest a cohort effect related to contaminated vaccines., Discussion: Association of SV40 with human MM is suggested from laboratory observations but still lacks confirmation in well designed epidemiological studies. Other putative co-factors in MM occurrence are mutations in genes involved in repair of damage caused by asbestos, notably DNA-repair genes. Preliminary observations are available but epidemiological studies are needed to test this hypothesis.

Background: Recent studies have reported detection of simian virus 40 (SV40) DNA in tumor tissues from 15%-43% of U.S. non-Hodgkin lymphoma (NHL) patients. SV40 accidentally contaminated U.S. poliovirus vaccines that were widely administered from 1955 through 1962. However, epidemiologic data linking SV40 with NHL are lacking., Methods: We obtained serum samples from 724 incident NHL case patients and 622 control subjects from a population-based U.S. case-control study. SV40 serostatus was analyzed by two independent laboratories (designated A and B) using similar virus-like particle (VLP) enzyme immunoassays. Associations with serostatus were assessed with logistic regression, adjusting for sex, race, birth year, and study site. VLPs for the human polyomaviruses BK and JC were used in competitive inhibition experiments to assess the specificity of SV40 reactivity. Statistical tests were two-sided., Results: SV40 antibody results from the two laboratories were correlated (R = 0.59; P<.001). Laboratories A and B detected SV40 seropositivity in 7.2% and 9.8% of NHL case patients, respectively, and in 10.5% and 9.6% of control subjects, respectively. SV40 seropositivity was not associated with increased NHL risk (laboratory A: adjusted odds ratio [OR] = 0.68, 95% confidence interval [CI] = 0.46 to 1.00; laboratory B: adjusted OR = 1.02, 95% CI = 0.71 to 1.47). SV40 seropositivity was not associated with NHLs of any specific histology or site. Among subjects born before 1963, 1.0%-1.6% showed SV40-specific reactivity, i.e., SV40 reactivity confirmed in competitive inhibition experiments, whereas (based on limited data) none born subsequently demonstrated SV40-specific reactivity., Conclusions: In persons born before 1963, the presence of SV40-specific antibodies, although rare, could reflect exposure to SV40-contaminated vaccines. Nevertheless, NHL risk was unrelated to serologic evidence of SV40 exposure or infection.