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Concept: Polyomaviruses

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Polyomaviruses are ubiquitous, species-specific viruses belonging to the family Papovaviridae. The two most commonly known human polyomaviruses, BK virus and JC virus were first described in the 1970s. Newer human polyomaviruses, namely KI polyoma virus, WU polyoma virus and Merkel cell polyoma virus were identified in the last five years. Most humans encounter BK and JC virus during childhood, causing mild illness. However, when reactivated or acquired in the immunocompromised host, BK and JC virus have been implicated in a number of human clinical disease states. BK is most commonly associated with renal involvement, such as ureteral stenosis, hemorrhagic cystitis and nephropathy. Less commonly, it is associated with pneumonitis, retinitis, liver disease and meningoencephalitis. JC virus is most well known for its association with progressive multifocal leukoencephalopathy, and is possibly implicated in the development of various human neoplasms. The following chapter will outline the basic virology, epidemiology and clinical manifestations of BK and JC virus and discuss relevant diagnostic and treatment options.

Concepts: AIDS, Virus, Viruses, Progressive multifocal leukoencephalopathy, BK virus, JC virus, Polyomavirus, Polyomaviruses

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Polyomaviruses, including simian virus 40 (SV40), display evidence of lymphotropic properties. This study analyzed the nature of SV40-human lymphocyte interactions in established cell lines and in primary lymphocytes. The effects of viral microRNA and the structure of the viral regulatory region on SV40 persistence were examined.

Concepts: Lymphocyte, DNA, Gene, Bacteria, Cytotoxicity, Polyomavirus, SV40, Polyomaviruses

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Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis other polyomavirus-associated diseases including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but if SV40 immunohistochemistry also cross-reacted with MCPyV that would be advantageous from a resource-utilization perspective.

Concepts: Neuroendocrine tumor, Progressive multifocal leukoencephalopathy, JC virus, Merkel cell cancer, Merkel cell, Polyomavirus, Merkel cell polyomavirus, Polyomaviruses

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Polyomaviruses are a family of small DNA tumor viruses that includes several pathogenic human members, including Merkel cell polyomavirus, BK virus and JC virus. As is characteristic of DNA tumor viruses, gene expression in polyomaviruses is temporally regulated into an early phase, consisting of the viral regulatory proteins, and a late phase, consisting of the viral structural proteins. Previously, the late transcripts expressed by the prototypic polyomavirus simian virus 40 (SV40) were reported to contain several adenosines bearing methyl groups at the N6 position (m6A), although the precise location of these m6A residues, and their phenotypic effects, have not been investigated. Here, we first demonstrate that overexpression of the key m6A reader protein YTHDF2 induces more rapid viral replication, and larger viral plaques, in SV40 infected BSC40 cells, while mutational inactivation of the endogenous YTHDF2 gene, or the m6A methyltransferase METTL3, has the opposite effect, thus suggesting a positive role for m6A in the regulation of SV40 gene expression. To directly test this hypothesis, we mapped sites of m6A addition on SV40 transcripts and identified two m6A sites on the viral early transcripts and eleven m6A sites on the late mRNAs. Using synonymous mutations, we inactivated the majority of the m6A sites on the SV40 late mRNAs and observed that the resultant viral mutant replicated more slowly than wild type SV40. Alternative splicing of SV40 late mRNAs was unaffected by the reduction in m6A residues and our data instead suggest that m6A enhances the translation of viral late transcripts. Together, these data argue that the addition of m6A residues to the late transcripts encoded by SV40 plays an important role in enhancing viral gene expression and, hence, replication.

Concepts: DNA, Gene, Gene expression, Microbiology, Virus, JC virus, Polyomavirus, Polyomaviruses

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Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV DNA sequences using a specific real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40 (SV40) in children from 0 to 3 years, to 91% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.

Concepts: Lymphatic system, Arithmetic mean, Mean, Standard deviation, JC virus, Polyomavirus, SV40, Polyomaviruses

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Introduction The family of polyomaviruses, which cause severe disease in immunocompromised hosts, has expanded substantially in recent years. To accommodate measurement of IgG seroresponses against all currently known human polyomavirus (HPyV), including the Lyon IARC polyomavirus (LIPyV), we extended our custom multiplex bead-based HPyV immunoassay and evaluated the performance of this pan-HPyV immunoassay.Methods VP1 protein of fifteen HPyVs belonging to 13 polyomavirus species were expressed as recombinant glutathione S-transferase (GST) fusion proteins and coupled to fluorescent Luminex beads. Sera from healthy blood donors and immunocompromised kidney transplant recipients were used to analyse seroreactivity against the different HPyVs. For BK polyomavirus (BKPyV) the GST-VP1 fusion protein-directed seroresponses were compared to those obtained against BKPyV VP1 virus-like particles (VLP).Results Seroreactivity against most HPyVs was common and generally high in both test populations. Low seroreactivity was observed against HPyV9, HPyV12, New Jersey PyV and LIPyV. The assay was reproducible (Pearson’s r2> 0.84, P<0.001) and specific. Weak but consistent cross-reactivity was observed between related HPyV6 and HPyV7. Seroresponses measured by the GST-VP1-based immunoassay and the VP1 VLP-based ELISA were highly correlated (Spearman's ρ=0.823, P<0.001).Conclusions The bead-based pan-HPyV multiplex immunoassay is a reliable tool to determine HPyV-specific seroresponses with high reproducibility and specificity and is suitable for seroepidemiological studies.

Concepts: Scientific method, Protein, Measurement, ELISA, Assay, BK virus, Polyomavirus, Polyomaviruses

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To identify decoy cells, cytological examination was performed in urine cytospin slides. Decoy cells are related to Polyomaviruses (JC virus [JCV] and BK virus [BKV]), which are recognized worldwide due to potential infection and morbidity in kidney transplantrecipients. Cytologically, it is difficult to evaluate the cytopathic effect of JC and BK virus in urine of patients with urothelial neoplasia. For this reason, there is a need for molecular approaches.

Concepts: DNA, Protein, Microbiology, Viruses, BK virus, JC virus, Polyomavirus, Polyomaviruses

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BK polyomavirus (BKPyV) reactivation is a common clinical occurrence in kidney transplant recipients (KTR). Several other polyomaviruses have been implicated as pathogens with a direct role in the development of malignancies, raising the question of whether BKPyV might also be oncogenic.

Concepts: Cohort study, Clinical trial, Bacteria, Squamous cell carcinoma, BK virus, JC virus, Polyomavirus, Polyomaviruses

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Human polyomaviruses such as JC polyomavirus and BK polyomavirus have long been well known pathogens of immunocompromised patients. Several new members of this viral family have been described during the last decade. Human polyomavirus 9 seems to be a novel pathogen of transplanted patients according to some studies. The study aim: The aim of our study was to determine the presence of human polyomavirus 9 in patients after kidney or stem cell transplantation at the University Hospital in Hradec Kralove, Czech Republic.

Concepts: Microbiology, Czech Republic, BK virus, JC virus, Polyomavirus, Hradec Králové, Polyomaviruses, Hradec Králové Region

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This study aimed to identify and quantify polyomaviruses (BKPyV and JCPyV) in the saliva, mouthwash, blood and urine of liver pre-transplant patients.

Concepts: Red blood cell, JC virus, Polyomaviruses