Presence Of Human Polyomaviruses Research Articles

Human polyomaviruses JCPyV and MCPyV in urothelial cell carcinoma: a single institution experience.

Urothelial cell carcinoma (UCC) is the most common type of urinary bladder. JCPyV and BKPyV have been detected in the urine and tissue of urothelial cell carcinomas (UCC) in immunocompetent patients. Here, we investigated the presence of several HPyVs in UCC samples using diverse molecular techniques to study the prevalence of HPyVs in UCC. A large single-institution database of urine cytology specimens (UCS; n = 22.867 UCS) has previously been searched for decoy cells (n = 30), suggesting polyomavirus infection. The available urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC patients were tested for the presence of JCPyV-LTAg expression by immunohistochemistry (IHC) labeled with SV40-LTAg antibody (clone: PAb416) and subsequent PCR followed by sequencing. In addition, the presence of the oncogenic Merkel cell polyomavirus (MCPyV) and the presence of human polyomavirus 6 (HPyV6) and 7 (HPyV7) DNA were tested with DNA PCR or IHC. Of the 30 patients harboring decoy cells, 14 were diagnosed with UCC of the urinary bladder (14/30; 46.6%) before presenting with decoy cells in the urine. The SV40-LTAg IHC was positive in all 14 UCC urine sediments and negative in the FFPE tissues. JCPyV-DNA was identified in all five available UCS and in three FFPE samples of UCC (three of 14; 21.4%). Two UCC cases were positive for MCPyV-DNA (two of 14; 14.3%), and one of them showed protein expression by IHC (one of 14; 7.1%). All specimens were HPyV6 and HPyV7 negative. Our findings show the presence of JCPyV in the urine and UCC of immunocompetent patients. Moreover, MCPyV was detected in two UCC cases. In total, five UCC cases showed the presence of either JCPyV or MCPyV. The evidence here supports the hypothesis that these viruses might sporadically be associated with UCC. Further studies are needed to confirm the relevance of JCPyV or MCPyV as a possible risk factor for UCC development.

The differential presence of human polyomaviruses, JCPyV and BKPyV, in prostate cancer and benign prostate hypertrophy tissues

BackgroundStudies have shown that human polyomavirus infection may be associated with various human cancers. We investigated the potential relationship between the prevalence of JCPyVor BKPyV and prostate cancer (PC) in patients from Taiwan.MethodsPatients with PC and benign prostate hypertrophy (BPH; 76 and 30 patients, respectively) were recruited for this study. Paraffin-embedded tissues and clinical information of the patients were obtained. The tissue sections were used for viral DNA detection and immunohistochemistry analysis was performed for examining viral large T (LT) and VP1 proteins. Regression analysis was used to evaluate the relationship between the clinical characteristics of the patients and the risk of JCPyV/BKPyV infection.ResultsThe prevalence of JCPyV/BKPyV DNA was different in PC and BPH tissues (27/76 [35.52%] and 2/30 [6.7%], respectively, p = 0.003)]. The LT and VP1 proteins were detected in 27 (35.52%) and 29 PC (38.2%) specimens, respectively, but neither protein was detected in BPH samples (p < 0.001). PC cells were more susceptible to JCPyV infection than BPH tissues [odds ratio (OR) 7.71, 95% CI: 1.71–34.09, p = 0.003). Patients with PC showing high levels of prostate-specific antigen and high Gleason scores were associated with a high risk of viral infection (ORs 1.1, 95% CI 1.000–1.003; p = 0.045 and ORs 6.18, 95% CI 1.26–30.33, p = 0.025, respectively). The expression of LT protein associated with the risk of PC increased 2923.39-fold (95% CI 51.19–166,963.62, p < 0.001).ConclusionsThe findings indicate that JCPyV infection in PC cells may be associated with prostate cancer progression and prognosis.Graphical abstract

Distribution and genetic diversity of the human polyomaviruses JC and BK in surface water and sewage treatment plant during 2009 in Porto Alegre, Southern Brazil

The human polyomaviruses JC and BK (JCPyV and BKPyV) are ubiquitous, species-specific viruses that belong to the family Polyomaviridae. These viruses are known to be excreted in human urine, and they are potential indicators of human wastewater contamination. In order to assess the distribution of both JCPyV and BKPyV in urban water samples collected from a sewage treatment plant (STP) and from a canalized water stream of Porto Alegre, Brazil, two nested-PCR assays were optimized and applied to the samples collected. The amplicons obtained were submitted to sequencing, and the sequences were analyzed with sequences of human polyomaviruses previously deposited in GenBank. Twelve out of 30 water samples (40%) were JCPyV positive, whereas six samples (20%) were BKPyV positive. The sequencing results confirmed the presence of JCPyV subtypes 1 and 3, whereas only BKPyV Ia and Ib were found. This study shows for the first time the presence of human polyomaviruses in surface water and in samples collected in a sewage treatment plant in southern Brazil.

Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced epithelial proliferations.

A frequent adverse effect of mutation-specific BRAF inhibitor therapy is the induction of epithelial proliferations including cutaneous squamous cell carcinomas. To date, the only factor identified contributing to their development is the activation of the mitogen-activated signal transduction cascade by mutations in the RAS genes. However, these mutations explain only 60% of the tumors; hence, it is important to identify what is causing the remaining tumors. To test for the presence of human papillomaviruses (HPVs) and the recently identified human polyomaviruses (HPyVs), Merkel cell polyomavirus (MCPyV), and trichodysplasia spinulosa-associated polyomavirus (TSPyV), as well as HPyV-6, HPyV-7, HPyV-9, and HPyV-10, in epithelial proliferations occurring after BRAF inhibitor therapy to determine whether these oncogenic viruses may contribute to BRAF inhibitor-induced skin tumors. Retrospective study at a university hospital in Austria of epithelial proliferations that developed in patients with melanoma after initiation of treatment with the BRAF inhibitor vemurafenib. Samples were analyzed for (1) presence of the most frequently observed RAS mutations by SNaPshot technology, (2) detection of the viruses by real-time polymerase chain reaction, and (3) presence of capsid proteins of the most abundantly detected virus by immunohistochemical analysis. RAS mutational status, as well as HPV and HPyV presence, in BRAF inhibitor-induced epithelial proliferations. Eighteen biopsy samples from 6 patients were retrieved from our hospital's archive. We identified RAS mutations in 10 (62%) of the 16 samples with clear results. DNA of HPyV-9, HPyV-10, and TSPyV were virtually absent in the samples. MCPyV DNA was present in 13 of 18 samples, and HPV, HPyV-6, and HPyV-7 DNA were present in all samples. In general, the amount of DNA encoding the latter viruses was rather low, with the exception of HPyV-6 in several samples of 1 individual patient. Notably, the relevance of the presence of HPyV-6 in the epithelial proliferation was underlined by immunohistochemical detection of the core protein VP1 of HPyV-6. The presence of both high HPyV-6 DNA load and VP1 protein suggests that polyomaviruses may contribute to the epithelial proliferations observed in patients receiving BRAF inhibitor therapy, albeit the relative impact as compared with that of RAS mutations appears circumstantial.

SPECIFIC VIRUSES WERE NOT DETECTED IN GUTHRIE CARDS FROM CHILDREN WHO LATER DEVELOPED LEUKEMIA

There are hypotheses concerning infectious mechanism in the development of acute lymphoblastic leukemia (ALL). The first genetic event often happens in utero, based on studies from Guthrie cards. The authors have summarized the results from their studies concerning infectious mechanism. Presence of human polyomaviruses, parvovirus, HHV-6, EBV, and CMV were investigated by PCR from Guthrie cards from children who later developed ALL and healthy controls. Neither of these viruses were detected from patients nor from controls. The results do not support that these viruses have contributed to the development of a substantial part of the ALL cases in Swedish children.

Polyomavirus viruria in bone marrow transplant recipients: lack of correlation with clinical symptoms.

Human polyomavirus (HPV) infection is controversially discussed as a factor influencing the outcome of bone marrow transplantation (BMT). Here we report on 62 patients undergoing BMT with clinical signs of urocystitis, such as micro- or macrohematuria with more or less severe dysuria. These patients were tested for the presence of HPV in urine specimens (n = 80) by transmission electron microscopy (TEM). HPV viruria was found in 35 patients (56%); 33 (94%) of them had hemorrhagic cystitis, whereas two (6%) were suffering from dysuria only. Among the patients with hemorrhagic cystitis, ten (30%) presented with macrohematuria, four (12%) with microhematuria and 19 (58%) with micro- or macrohematuria and severe dysuria. 26 of 27 HPV-negative patients (96%) showed hemorrhagic cystitis with either macrohematuria (n = 7) (26%) or microhematuria (n = 15) (56%). Four patients (15%) suffered from hematuria and dysuria, one patient (4%) from dysuria only. Although HPV-negative patients tended to present with less severe clinical symptoms, overall no statistically significant influence on the outcome of BMT was seen.