Potential Transmission of Human Polyomaviruses through the Gastrointestinal Tract after Exposure to Virions or Viral DNA

ABSTRACT The mechanism of human-to-human transmission of the polyomaviruses JC virus (JCV) and BK virus (BKV) has not been firmly established with regard to possible human exposure. JCV and BKV have been found in sewage samples from different geographical areas in Europe, Africa, and the United States, with average concentrations of 102 to 103 JCV particles/ml and 101 to 102BKV particles/ml. Selected polyomavirus-positive sewage samples were further characterized. The JCV and BKV present in these samples were identified by sequencing of the intergenic region (the region found between the T antigen and VP coding regions) of JCV and the VP1 region of BKV. The regulatory region of the JCV and BKV strains found in sewage samples presented archetypal or archetype-like genetic structures, as described for urine samples. The stability (the time required for a 90% reduction in the virus concentration) of the viral particles in sewage at 20°C was estimated to be 26.7 days for JCV and 53.6 days for BKV. The presence of JCV in 50% of the shellfish samples analyzed confirmed the stability of these viral particles in the environment. BKV and JCV particles were also found to be stable at pH 5; however, treatment at a pH lower than 3 resulted in the detection of free viral DNA. Since most humans are infected with JCV and BKV, these data indicate that the ingestion of contaminated water or food could represent a possible portal of entrance of these viruses or polyomavirus DNA into the human population.

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Quantification of Human Polyomaviruses JC Virus and BK Virus by TaqMan Quantitative PCR and Comparison to Other Water Quality Indicators in Water and Fecal Samples

Applied and Environmental Microbiology ◽

10.1128/aem.02302-08 ◽

2009 ◽

Vol 75 (11) ◽

pp. 3379-3388 ◽

Cited By ~ 154

Author(s):

Shannon M. McQuaig ◽

Troy M. Scott ◽

Jerzy O. Lukasik ◽

John H. Paul ◽

Valerie J. Harwood

Keyword(s):

Water Quality ◽

Quantitative Pcr ◽

Jc Virus ◽

The United States ◽

T Antigen ◽

Bk Virus ◽

Qpcr Assay ◽

Gene Copies ◽

Bodies Of Water ◽

Human Polyomaviruses

ABSTRACT In the United States, total maximum daily load standards for bodies of water that do not meet bacterial water quality standards are set by each state. The presence of human polyomaviruses (HPyVs) can be used as an indicator of human-associated sewage pollution in these waters. We have developed and optimized a TaqMan quantitative PCR (QPCR) assay based on the conserved T antigen to both quantify and simultaneously detect two HPyVs; JC virus and BK virus. The QPCR assay was able to consistently quantify ≥10 gene copies per reaction and is linear over 5 orders of magnitude. HPyVs were consistently detected in human waste samples (57 of 64) and environmental waters with known human fecal contamination (5 of 5) and were not amplified in DNA extracted from 127 animal waste samples from 14 species. HPyV concentrations in sewage decreased 81.2 and 84.2% over 28 days incubation at 25 and 35°C, respectively. HPyVs results were compared to Escherichia coli, fecal coliform, and enterococci concentrations and the presence of three other human-associated microbes: Bacteroidetes, Methanobrevibacter smithii, and adenovirus. HPyVs were the most frequently detected of these in human and contaminated environmental samples and were more human specific than the Bacteroidetes (HF183) or M. smithii. HPyVs and M. smithii more closely mimicked the persistence of adenovirus in sewage than the other microbes. The use of this rapid and quantitative assay in water quality research could help regulatory agencies to identify sources of water pollution for improved remediation of contaminated waters and ultimately protect humans from exposure to pathogens.

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A correlation study of BK Polyoma Virus infection and prostate Cancer among Sudanese patients - immunofluorescence and molecular based case-control study

Infectious Agents and Cancer ◽

10.1186/s13027-019-0244-7 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Babbiker Mohammed Taher Gorish ◽

Mohammed Elfatih Hussein Ournasseir ◽

Iman Mohammed Shammat

Keyword(s):

Prostate Cancer ◽

Viral Load ◽

Case Control ◽

T Antigen ◽

Bk Virus ◽

Direct Immunofluorescence ◽

Conventional Pcr ◽

Viral Dna ◽

Predisposing Factor ◽

Tissue Specimens

Abstract Background Polyomavirus hominis1, also called BK virus (BKV) is a well-known etiological agent of renal transplant nephropathy and cystitis. Recently, it got great attention from the researcher as a principal predisposing factor for different kinds of cancers including prostate cancer (PCa). Thus, this study aims to determine the correlation between BKV infection and PCa through a descriptive case-control based study. Methods A total of 55 paraffin-embedded tissue blocks of patients with PCa and another 55 tissue blocks from BPH patients were obtained. In parallel, respective urine samples were collected from all the cases and controls. The existence of BKV large T antigen (LTAg) was analyzed by Direct Immunofluorescence assay. Only BKV LTAg positive specimens were further analyzed for the presence of viral DNA by using a conventional PCR then subjected to viral load quantitation by using Q-PCR. Result BKV LTAg was identified in 30% (17/55) of cases tissue specimens and only in 7% (4/55) of the controls tissue specimens with P-value 0.002 and Odd ratio 5.7. The conventional PCR detects the BKV DNA in 16 out of 17 cases specimens while only two out of four controls specimens were identified with a viral DNA. The mean of the BKV DNA load was higher significantly among cases 6733 ± 6745 copies/ml when compared to controls 509.0 ± 792.9 copies/m with a p-value of 0.002. Conclusion More BKV prevalence with high viral load was observed in PCa patients tissue compared to BPH specimens. PCa Gleason scores 9 and 7 were the most cancer grades identified with the presence of BKV DNA. Our findings are thus consistent with a significant link between the BKV infection and the PCa risk. Prostate or seminal fluids should be selected as principal specimens for future studies and can, therefore, be designated as screening samples to find early virus evidence in the prostate tissue. Detection of early virus evidence may help to reduce the risk of PCa cancer due to BKV.

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Regulation of Gene Expression in Primate Polyomaviruses

Journal of Virology ◽

10.1128/jvi.00542-09 ◽

2009 ◽

Vol 83 (21) ◽

pp. 10846-10856 ◽

Cited By ~ 70

Author(s):

Martyn K. White ◽

Mahmut Safak ◽

Kamel Khalili

Keyword(s):

Gene Expression ◽

Jc Virus ◽

Regulation Of Gene Expression ◽

T Antigen ◽

Bk Virus ◽

Viral Gene ◽

Cell Type ◽

Cell Type Specificity ◽

Karolinska Institute ◽

Human Polyomaviruses

ABSTRACT Polyomaviruses are a growing family of small DNA viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. Species host range may be constrained by requirements for precise molecular interactions between the viral T antigen, host replication proteins, including DNA polymerase, and the viral origin of replication, which are required for viral DNA replication. Cell type specificity involves, at least in part, transcription factors that are necessary for viral gene expression and restricted in their tissue distribution. In the case of the human polyomaviruses, BK virus (BKV) replication occurs in the tubular epithelial cells of the kidney, causing nephropathy in kidney allograft recipients, while JC virus (JCV) replication occurs in the glial cells of the central nervous system, where it causes progressive multifocal leukoencephalopathy. Three new human polyomaviruses have recently been discovered: MCV was found in Merkel cell carcinoma samples, while Karolinska Institute Virus and Washington University Virus were isolated from the respiratory tract. We discuss control mechanisms for gene expression in primate polyomaviruses, including simian vacuolating virus 40, BKV, and JCV. These mechanisms include not only modulation of promoter activities by transcription factor binding but also enhancer rearrangements, restriction of DNA methylation, alternate early mRNA splicing, cis-acting elements in the late mRNA leader sequence, and the production of viral microRNA.

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Analysis of 15 novel full-length BK virus sequences from three individuals: evidence of a high intra-strain genetic diversity

Journal of General Virology ◽

10.1099/vir.0.79920-0 ◽

2004 ◽

Vol 85 (9) ◽

pp. 2651-2663 ◽

Cited By ~ 44

Author(s):

Yiping Chen ◽

Paul M. Sharp ◽

Mary Fowkes ◽

Olivier Kocher ◽

Jeffrey T. Joseph ◽

...

Keyword(s):

Striated Muscle ◽

Jc Virus ◽

Regulatory Region ◽

Bk Virus ◽

Full Length ◽

Human Polyomavirus ◽

Coding Region ◽

Nucleotide Substitutions ◽

Source Of Infection

To determine the variability of BK virus (BKV) in vivo, the sequences of nine full-length molecular clones from the striated muscle and heart DNA of a patient with BKV-associated capillary leak syndrome (BKVCAP), as well as three clones each from the urine of one human immunodeficiency virus type 2-positive (BKVHI) and one healthy control subject (BKVHC), were analysed. The regulatory region of all clones corresponded to the archetypal regulatory region usually found in urine isolates. Analysis of the predicted conformation of BKVCAP proteins did not suggest any structural differences on the surface of the viral particles compared with BKVHI and BKVHC clones. No amino acid changes common to most BKVCAP clones could be identified that have not already been reported in non-vasculotropic strains. However, the coding region of each clone had unique nucleotide substitutions, and intra-host variability was greater among BKVCAP clones, with a mean difference of 0·29 % per site compared with 0·16 % for BKVHI and 0·14 % for BKVHC. The clones from each strain formed monophyletic clades, suggesting a single source of infection for each subject. The most divergent BKVCAP clones differed at 0·55 % of sites, implying a rate of nucleotide substitution of approximately 5×10−5 substitutions per site per year, which is two orders of magnitude faster than estimated for the other human polyomavirus, JC virus.

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Large T-Antigen and Sequences within the Regulatory Region of JC Virus Both Contribute to the Features of JC Virus DNA Replication

Virology ◽

10.1006/viro.1993.1627 ◽

1993 ◽

Vol 197 (2) ◽

pp. 537-548 ◽

Cited By ~ 16

Author(s):

Elisabeth Sock ◽

Michael Wegner ◽

Elizabeth A. Fortunato ◽

Friedrich Grummt

Keyword(s):

Dna Replication ◽

Jc Virus ◽

Regulatory Region ◽

T Antigen ◽

Large T Antigen

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BK Virus RNA in Renal Allograft Biopsies

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420922604 ◽

2020 ◽

Vol 68 (5) ◽

pp. 319-325 ◽

Cited By ~ 1

Author(s):

Francesca Costigliolo ◽

Kara Lombardo ◽

Lois J. Arend ◽

Avi Z. Rosenberg ◽

Andres Matoso ◽

...

Keyword(s):

Renal Allograft ◽

Jc Virus ◽

Graft Loss ◽

T Antigen ◽

Bk Virus ◽

Kidney Transplant Recipients ◽

Sv40 Large T Antigen ◽

Virus Rna ◽

Allograft Biopsy ◽

Alternative Test

BK polyomavirus–associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC ( R2 = 0.65, p<0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.

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T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus

Journal of General Virology ◽

10.1099/vir.0.82094-0 ◽

2006 ◽

Vol 87 (10) ◽

pp. 2951-2960 ◽

Cited By ~ 51

Author(s):

Jongming Li ◽

Jos Melenhorst ◽

Nancy Hensel ◽

Katyoun Rezvani ◽

Giuseppe Sconocchia ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Jc Virus ◽

Sequence Similarity ◽

Simian Virus 40 ◽

T Cell Responses ◽

T Antigen ◽

Bk Virus ◽

Cell Responses ◽

Cross Immunity

Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and II T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses.

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JC virus T' proteins encoded by alternatively spliced early mRNAs enhance T antigen-mediated viral DNA replication in human cells

Journal of NeuroVirology ◽

10.1080/13550280152403290 ◽

2001 ◽

Vol 7 (3) ◽

pp. 250-264 ◽

Cited By ~ 36

Author(s):

Cindy Prins, Richard J Frisque

Keyword(s):

Dna Replication ◽

Jc Virus ◽

T Antigen ◽

Human Cells ◽

Viral Dna ◽

Viral Dna Replication ◽

Alternatively Spliced

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Restriction of Human Polyomavirus BK Virus DNA Replication in Murine Cells and Extracts

Journal of Virology ◽

10.1128/jvi.00300-09 ◽

2009 ◽

Vol 83 (11) ◽

pp. 5708-5717 ◽

Cited By ~ 11

Author(s):

Cathal Mahon ◽

Bo Liang ◽

Irina Tikhanovich ◽

Johanna R. Abend ◽

Michael J. Imperiale ◽

...

Keyword(s):

Dna Replication ◽

Topoisomerase I ◽

Simian Virus 40 ◽

T Antigen ◽

Bk Virus ◽

Human Polyomavirus ◽

Expression Vectors ◽

Viral Dna ◽

Viral Dna Replication ◽

Cell Extracts

ABSTRACT BK virus (BKV) causes persistent and asymptomatic infections in most humans and is the etiologic agent of polyomavirus-associated nephropathy (PVAN) and other pathologies. Unfortunately, there are no animal models with which to study activation of BKV replication in the human kidney and the accompanying PVAN. Here we report studies of the restriction of BKV replication in murine cells and extracts and the cause(s) of this restriction. Upon infection of murine cells, BKV expressed large T antigen (TAg), but viral DNA replication and progeny were not detected. Transfection of murine cells with BKV TAg expression vectors also caused TAg expression without accompanying DNA replication. Analysis of the replication of DNAs containing chimeric BKV and murine polyomavirus origins revealed the importance of BKV core origin sequences and TAg for DNA replication. A sensitive assay was developed with purified BKV TAg that supported TAg-dependent BKV DNA replication with human but not with murine cell extracts. Addition of human replication proteins, DNA polymerase α-primase, replication protein A, or topoisomerase I to the murine extracts with BKV TAg did not rescue viral DNA replication. Notably, addition of murine extracts to human extracts inhibited BKV TAg-dependent DNA replication at a step prior to or during unwinding of the viral origin. These findings and differences in replication specificity between BKV TAg and the TAgs of simian virus 40 (SV40) and JC virus (JCV) and their respective origins implicate features of the BKV TAg and origin distinct from SV40 and JCV in restriction of BKV replication in murine cells.

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