Kean JM, Rao S, Wang M, Garcea RLSeroepidemiology of human polyomaviruses. PLoS Pathog 5: e1000363

Department of Microbiology, University of Colorado School of Medicine, Denver, Colorado, USA.
PLoS Pathogens (Impact Factor: 7.56). 04/2009; 5(3):e1000363. DOI: 10.1371/journal.ppat.1000363
Source: PubMed

ABSTRACT In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/- 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was approximately 2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood.

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Available from: Suchitra Rao, Nov 18, 2014
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    • "Primary BKV and JCV infections are nonsevere, but the viruses remain latent in the organism. Although high seroprevalences of 80–90% for BKV and up to 50–60% for JCV in the healthy population have been reported [10] [11], severe consequences of virus reactivation among immunocompetent individuals are rare. Signs of polyomavirus reactivation are typically obtained only after the onset of severe disease symptoms. "
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    ABSTRACT: BK and JC polyomaviruses encode microRNAs which may facilitate the establishment of persistent infection. MicroRNAs contribute to disease pathogenesis, and may provide useful tools in laboratory diagnostics and patient management. In this pilot work we studied whether viral and cellular microRNAs can be extracted and detected from body fluids to provide added value in a diagnostic laboratory. Altogether 120 human plasma, urine, and cerebrospinal fluid samples from individuals diagnosed with, or suspected of, a severe polyomavirus associated disease, were included in the study. The samples were spiked with unrelated synthetic microRNA to control for sample quality and inhibition. BKV specific bkv-miR-B1-5p, JCV specific jcv-miR-J1-5p, and bkv-miR-B1-3p/jcv-miR-J1-3p, sharing identical sequences between the two viruses, were amplified from human samples using specific TaqMan assays. Expression of 84 circulating human microRNAs was studied in four selected plasma samples in microarray. jcv-miR-J1-5p and bkv-miR-B1-3p/jcv-miR-J1-3p were frequently amplified from human plasma, urine, and cerebrospinal fluid samples. bkv-miR-B1-5p was amplified from one-third of the samples, which often contained high viral DNA loads. A microarray screen of human microRNAs in plasma samples suggested regulation of several human microRNA expression in BKV positive vs negative samples. Viral and cellular microRNAs can be processed and detected from human body fluids. They may prove useful in the diagnosis and management of severe polyomavirus associated diseases, calling for further clinical evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 04/2015; 65. DOI:10.1016/j.jcv.2015.01.019 · 3.02 Impact Factor
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    • "JCV is a ubiquitous virus that infects a large proportion of the general population. According to sero-epidemiological studies, primary infection with JCV occurs in early childhood and over 70–90% of adult individuals are positive for anti-JCV antibodies [13], [14]. Although primary infection is asymptomatic, the proposed route of transmission is via the respiratory tract, after which JCV establishes a latent infection in the kidney. "
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    ABSTRACT: During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein β-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear β-catenin in colon cancer cases and the effects of this complex in the activation of the transcription and cell cycle regulators c-Myc and Cyclin D1 in vitro. Gene amplification demonstrated the presence of viral sequences in 82.4% of cases and we detected expression of T-Antigen in 64.6% of cases by immunohistochemistry. Further, we found that T-Antigen and β-catenin co-localized in the nuclei of tumor cells and we confirmed the physical binding between these two proteins in vitro. The nuclear presence of T-Antigen and β-catenin resulted in the significant enhancement of TCF-dependent promoter activity and activation of the β-catenin downstream targets, c-Myc and Cyclin D1. These observations provide further evidence for a role of JCV T-Antigen in the dysregulation of the Wnt signaling pathway and in the pathogenesis of colon cancer.
    PLoS ONE 09/2014; 9(9):e106257. DOI:10.1371/journal.pone.0106257 · 3.23 Impact Factor
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    • "Differences were observed with respect to the intensity of virus-specific seroreactivities among seropositive individuals. Whereas MCPyV, HPyV6 and HPyV7 seroreactivity moderately increased with age, the seroreactivity for TSPyV rapidly increased, analogous to BKPyV seroreactivity, as reported also by others [23], [40], [41]. Advancing adult age correlated with a gradual decrease of seroreactivity for both TSPyV and BKPyV. "
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    ABSTRACT: The polyomavirus family is rapidly expanding with twelve new human viruses identified since 2007. A significant number of the new human polyomaviruses (HPyV) has been found on the skin. Whether these viruses share biological properties and should be grouped together is unknown. Here we investigated the serological behavior of cutaneous HPyVs in a general population. 799 sera from immunocompetent Australian individuals aged between 0-87 were analyzed with a Luminex xMAP technology-based immunoassay for the presence of VP1-directed IgG antibodies against MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and BKPyV as a control. Except for HPyV9, overall seropositivity was high for the cutanous polyomaviruses (66-81% in adults), and gradually increased with age. Children below 6 months displayed seropositivity rates comparable to the adults, indicative of maternal antibodies. TSPyV seroreactivity levels strongly increased after age 2 and waned later in life comparable to BKPyV, whereas MCPyV, HPyV6 and HPyV7 seroreactivity remained rather stable throughout. Based on the identified serologic profiles, MCPyV seems to cluster with HPyV6 and HPyV7, and TSPyV and HPyV9 by themselves. These profiles indicate heterogeneity among cutaneous polyomaviruses and probably reflect differences in exposure and pathogenic behavior of these viruses.
    PLoS ONE 11/2013; 8(11):e81078. DOI:10.1371/journal.pone.0081078 · 3.23 Impact Factor
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