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Robert L Garcea - One of the best experts on this subject based on the ideXlab platform.

  • structure analysis of the major capsid proteins of human Polyomaviruses 6 and 7 reveals an obstructed sialic acid binding site
    Journal of Virology, 2014
    Co-Authors: L J Stroh, Robert L Garcea, Barbel S Blaum, Ursula Neu, Michael H C Buch, Thilo Stehle
    Abstract:

    Human polyomavirus 6 (HPyV6) and HPyV7 are commonly found on human skin. We have determined the X-ray structures of their major capsid protein, VP1, at resolutions of 1.8 and 1.7 Å, respectively. In Polyomaviruses, VP1 commonly determines antigenicity as well as cell-surface receptor specificity, and the protein is therefore linked to attachment, tropism, and ultimately, viral pathogenicity. The structures of HPyV6 and HPyV7 VP1 reveal uniquely elongated loops that cover the bulk of the outer virion surfaces, obstructing a groove that binds sialylated glycan receptors in many other Polyomaviruses. In support of this structural observation, interactions of VP1 with α2,3- and α2,6-linked sialic acids could not be detected in solution by nuclear magnetic resonance spectroscopy. Single-cell binding studies indicate that sialylated glycans are likely not required for initial attachment to cultured human cells. Our findings establish distinct antigenic properties of HPyV6 and HPyV7 capsids and indicate that these two viruses engage nonsialylated receptors. IMPORTANCE Eleven new human Polyomaviruses, including the skin viruses HPyV6 and HPyV7, have been identified during the last decade. In contrast to better-studied Polyomaviruses, the routes of infection, cell tropism, and entry pathways of many of these new viruses remain largely mysterious. Our high-resolution X-ray structures of major capsid proteins VP1 from HPyV6 and from HPyV7 reveal critical differences in surface morphology from those of all other known polyomavirus structures. A groove that engages specific sialic acid-containing glycan receptors in related Polyomaviruses is obstructed, and VP1 of HPyV6 and HPyV7 does not interact with sialylated compounds in solution or on cultured human cells. A comprehensive comparison with other structurally characterized polyomavirus VP1 proteins enhances our understanding of molecular determinants that underlie receptor specificity, antigenicity, and, ultimately, pathogenicity within the polyomavirus family and highlight the need for structure-based analysis to better define phylogenetic relationships within the growing polyomavirus family and perhaps also for other viruses.

  • a cornucopia of human Polyomaviruses
    Nature Reviews Microbiology, 2013
    Co-Authors: James A Decaprio, Robert L Garcea
    Abstract:

    In recent years, nine new human Polyomaviruses have been discovered, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. DeCaprio and Garcea compare and contrast these new human viruses and discuss how they might interact with their human host.

  • wu and ki polyomavirus infections in pediatric hematology oncology patients with acute respiratory tract illness
    Journal of Clinical Virology, 2011
    Co-Authors: Robert L Garcea, Christine C Robinson, Eric A F Simoes
    Abstract:

    Background WU and KI Polyomaviruses (PyV) were discovered in 2007 in respiratory tract samples in adults and children. Other Polyomaviruses (BKPyV and JCPyV) have been associated with illness in immunocompromised patients, and some studies suggest a higher prevalence of WUPyV and KIPyV in this population.

  • seroepidemiology of human Polyomaviruses
    PLOS Pathogens, 2009
    Co-Authors: Jaime M Kean, Michael Wang, Robert L Garcea
    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 ∼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.

  • seroepidemiology of human Polyomaviruses
    PLOS Pathogens, 2009
    Co-Authors: Jaime M Kean, Michael Wang, Robert L Garcea, Suchitra Rao
    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.

Bernhard Ehlers - One of the best experts on this subject based on the ideXlab platform.

  • Multiple DNA viruses identified in multimammate mouse (Mastomys natalensis) populations from across regions of sub-Saharan Africa
    Archives of Virology, 2020
    Co-Authors: Sébastien Calvignac-spencer, Léonce Kouadio, Emmanuel Couacy-hymann, Nafomon Sogoba, Kyle Rosenke, Andrew J. Davison, Fabian Leendertz, Michael A. Jarvis, Heinz Feldmann, Bernhard Ehlers
    Abstract:

    The multimammate mouse ( Mastomys natalensis; M. natalensis ) serves as the main reservoir for the zoonotic arenavirus Lassa virus (LASV), and this has led to considerable investigation into the distribution of LASV and other related arenaviruses in this host species. In contrast to the situation with arenaviruses, the presence of other viruses in M. natalensis remains largely unexplored. In this study, herpesviruses and Polyomaviruses were identified and partially characterized by PCR methods, sequencing, and phylogenetic analysis. In tissues sampled from M. natalensis populations in Côte d ' Ivoire and Mali, six new DNA viruses (four betaherpesviruses, one gammaherpesvirus and one polyomavirus) were identified. Phylogenetic analysis based on glycoprotein B amino acid sequences showed that the herpesviruses clustered with cytomegaloviruses and rhadinoviruses of multiple rodent species. The complete circular genome of the newly identified polyomavirus was amplified by PCR. Amino acid sequence analysis of the large T antigen or VP1 showed that this virus clustered with a known polyomavirus from a house mouse (species Mus musculus polyomavirus 1 ). These two Polyomaviruses form a clade with other rodent Polyomaviruses, and the newly identified virus represents the third known polyomavirus of M. natalensis . This study represents the first identification of herpesviruses and the discovery of a novel polyomavirus in M. natalensis . In contrast to arenaviruses, we anticipate that these newly identified viruses represent a low zoonotic risk due to the normally highly restricted specificity of members of these two DNA virus families to their individual mammalian host species.

  • biology evolution and medical importance of Polyomaviruses an update
    Infection Genetics and Evolution, 2017
    Co-Authors: Ugo Moens, Reimar Johne, Bernhard Ehlers, Andi Krumbholz, Roland Zell, Sebastien Calvignacspencer, Chris Lauber
    Abstract:

    The family Polyomaviridae encompasses non-enveloped viruses with a circular dsDNA genome that is typically approximately 5000bp in length. Originally isolated from mammals, polyomavirus sequences have now been detected in invertebrates, fish, amphibians, reptiles and birds, although it remains to be determined whether all these animals are genuine hosts. The genomes of all Polyomaviruses encode at least two regulatory proteins (large and small tumour antigen) and two structural proteins (capsid proteins VP1 and VP2) whose functions have been defined. The large and small tumour antigens have domains conserved among the Polyomaviruses, which are responsible for specific interactions with cellular proteins and may result in alteration of the cell cycle. Additional open reading frames (ORFs) are present in the genomes of the different polyomavirus species. Some of these ORFs are transcribed and translated in viral proteins, but their functions remain poorly understood. Polyomaviruses have a restricted host specificity. This may indicate that co-divergence with their hosts, which has been demonstrated in a few cases, was an important factor during polyomavirus diversification. However, a strict co-divergence scenario fails to explain family-wide patterns of diversity, suggesting an important contribution of lineage duplication and, possibly to a lesser extent, recombination and cross-species transmission. Polyomaviruses are pathogens that can cause various malignant and non-malignant diseases in birds and mammals, including humans, but so far they have not been linked to disease in lower vertebrates. In immunosuppressed individuals, reactivation of polyomavirus BK or JC can cause serious disease of the urogenital tract and brain, respectively, while Merkel cell polyomavirus is most probably associated with the development of a highly aggressive neuroendocrine skin tumour in elderly or patients with pre-existing conditions. This review provides an update on the life cycle, prevalence, disease association, and evolution of the viruses belonging to this family.

  • assessing host virus codivergence for close relatives of merkel cell polyomavirus infecting african great apes
    Journal of Virology, 2016
    Co-Authors: Nadege Freda Madinda, Bernhard Ehlers, Joel O Wertheim, Chantal Akouakoffi, Richard A Bergl, Christophe Boesch, Dieudonne Boji Mungu Akonkwa, Winnie Eckardt, Barbara Fruth, Thomas R Gillespie
    Abstract:

    It has long been hypothesized that Polyomaviruses (PyV;family Polyomaviridae) codiverged with their animal hosts. In contrast, recent analyses suggested that codivergence may only marginally influence the evolution of PyV. We reassess this question by focusing on a single lineage of PyV infecting hominine hosts, the Merkel cell polyomavirus (MCPyV) lineage. By characterizing the genetic diversity of these viruses in seven African great ape taxa, we show that they exhibit very strong host specificity. Reconciliation analyses identify more codivergence than noncodivergence events. In addition, we find that a number of host and PyV divergence events are synchronous. Collectively, our results support codivergence as the dominant process at play during the evolution of the MCPyV lineage. More generally, our results add to the growing body of evidence suggesting an ancient and stable association of PyV and their animal hosts. IMPORTANCE The processes involved in viral evolution and the interaction of viruses with their hosts are of great scientific interest and public health relevance. It has long been thought that the genetic diversity of double-stranded DNA viruses was generated over long periods of time, similar to typical host evolutionary timescales. This was also hypothesized for Polyomaviruses ( family Polyomaviridae), a group comprising several human pathogens, but this remains a point of controversy. Here, we investigate this question by focusing on a single lineage of Polyomaviruses that infect both humans and their closest relatives, the African great apes. We show that these viruses exhibit considerable host specificity and that their evolution largely mirrors that of their hosts, suggesting that codivergence with their hosts played a major role in their diversification. Our results provide statistical evidence in favor of an association of Polyomaviruses and their hosts over millions of years.

  • genome sequence of a central chimpanzee associated polyomavirus related to bk and jc Polyomaviruses pan troglodytes troglodytes polyomavirus 1
    Genome Announcements, 2015
    Co-Authors: Bernhard Ehlers, Nadege Freda Madinda, Christophe Boesch, Martha M Robbins, Fabian H Leendertz, Sebastien Calvignacspencer
    Abstract:

    ABSTRACT We amplified and sequenced the genome of a polyomavirus infecting a central chimpanzee (Pan troglodytestroglodytes). This virus, which is closely related to BK and JC Polyomaviruses, may help shed a new light on these human pathogens’ evolutionary history.

  • the novel human Polyomaviruses hpyv6 7 9 and beyond
    Apmis, 2013
    Co-Authors: Bernhard Ehlers, Ulrike Wieland
    Abstract:

    Since the discovery of Merkel cell polyomavirus and its causative association with Merkel cell carcinoma (MCC), six human Polyomaviruses (HPyVs) have been identified that, so far, lack any disease association, which include the human Polyomaviruses (HPyV) 6, 7, 9, 10 and 12 as well as the Saint Louis polyomavirus (STLPyV). PCR studies revealed that HPyV6 and HPyV7 are shed from the skin of healthy subjects and of patients suffering from various skin tumours. HPyV6, 7 and 9 were sporadically detected in body fluids and excretions of immunocompromised patients and healthy subjects. HPyV10 was identified in papillomavirus-induced anal condylomas, and variants of HPyV10, named MWPyV and MX polyomavirus (human) (MXPyV), as well as STLPyV were detected in faeces of diarrheal and healthy children. HPyV12 was discovered in organs of the digestive tract of patients suffering from various malignant diseases. Serological studies using capsomer-based or virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) revealed that HPyV6, 7, 9 and 12 are circulating in the human population. As all other HPyVs, the novel Polyomaviruses encode small and large T antigens and thus are potentially oncogenic. However, several studies have revealed a lack of association of HPyV6, 7 and 9 with numerous human tumours. In the future, it will be important to unravel the cell types and body compartments of the novel HPyVs′ reservoir and to search for possible associations with cancer and non-malignant diseases.

Ugo Moens - One of the best experts on this subject based on the ideXlab platform.

  • Human Polyomaviruses and Papillomaviruses
    'MDPI AG', 2018
    Co-Authors: Ugo Moens
    Abstract:

    The interest in human Polyomaviruses (HPyV) has seen a renaissance because of new species that have been isolated and their previously unknown association with diseases. Likewise, the increasing evidence for the association of human papillomaviruses (HPV) with oropharyngeal cancer has sparked the attention of researchers and clinicians. The Special Issue “Human Polyomaviruses and Papillomaviruses” presents studies describing the nuclear egress of BK polyomavirus mediated by the viral agnoprotein and the cellular -SNAP protein. In addition, a study examines the promoter activity of two different variants of human polyomavirus 9 in different cell lines. This Special Issue offers an interesting perspective on the epidemiology of HR-HPV in different cancers and on the mechanisms by which these viruses target host cell proteins to replicate their genome, express their genes, interfere with autophagy, and induce cancer. Other topics that are highlighted include the role of co-factors, such as smoking and co-infection, novel therapeutic strategies, and surface immunoregulatory proteins, chemokines, and cytokines as possible biomarkers to determine the stage of a tumor and to predict clinical outcomes

  • biology evolution and medical importance of Polyomaviruses an update
    Infection Genetics and Evolution, 2017
    Co-Authors: Ugo Moens, Reimar Johne, Bernhard Ehlers, Andi Krumbholz, Roland Zell, Sebastien Calvignacspencer, Chris Lauber
    Abstract:

    The family Polyomaviridae encompasses non-enveloped viruses with a circular dsDNA genome that is typically approximately 5000bp in length. Originally isolated from mammals, polyomavirus sequences have now been detected in invertebrates, fish, amphibians, reptiles and birds, although it remains to be determined whether all these animals are genuine hosts. The genomes of all Polyomaviruses encode at least two regulatory proteins (large and small tumour antigen) and two structural proteins (capsid proteins VP1 and VP2) whose functions have been defined. The large and small tumour antigens have domains conserved among the Polyomaviruses, which are responsible for specific interactions with cellular proteins and may result in alteration of the cell cycle. Additional open reading frames (ORFs) are present in the genomes of the different polyomavirus species. Some of these ORFs are transcribed and translated in viral proteins, but their functions remain poorly understood. Polyomaviruses have a restricted host specificity. This may indicate that co-divergence with their hosts, which has been demonstrated in a few cases, was an important factor during polyomavirus diversification. However, a strict co-divergence scenario fails to explain family-wide patterns of diversity, suggesting an important contribution of lineage duplication and, possibly to a lesser extent, recombination and cross-species transmission. Polyomaviruses are pathogens that can cause various malignant and non-malignant diseases in birds and mammals, including humans, but so far they have not been linked to disease in lower vertebrates. In immunosuppressed individuals, reactivation of polyomavirus BK or JC can cause serious disease of the urogenital tract and brain, respectively, while Merkel cell polyomavirus is most probably associated with the development of a highly aggressive neuroendocrine skin tumour in elderly or patients with pre-existing conditions. This review provides an update on the life cycle, prevalence, disease association, and evolution of the viruses belonging to this family.

  • the role of merkel cell polyomavirus and other human Polyomaviruses in emerging hallmarks of cancer
    Viruses, 2015
    Co-Authors: Ugo Moens, Kashif Rasheed, Ibrahim Afolabi Abdulsalam, Baldur Sveinbjornsson
    Abstract:

    Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals, including humans. All Polyomaviruses encode the large T-antigen and small t-antigen proteins that share conserved functional domains, comprising binding motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. At present, 13 different human Polyomaviruses are known, and for some of them their large T-antigen and small t-antigen have been shown to possess oncogenic properties in cell culture and animal models, while similar functions are assumed for the large T- and small t-antigen of other human Polyomaviruses. However, so far the Merkel cell polyomavirus seems to be the only human polyomavirus associated with cancer. The large T- and small t-antigen exert their tumorigenic effects through classical hallmarks of cancer: inhibiting tumor suppressors, activating tumor promoters, preventing apoptosis, inducing angiogenesis and stimulating metastasis. This review elaborates on the putative roles of human Polyomaviruses in some of the emerging hallmarks of cancer. The reciprocal interactions between human Polyomaviruses and the immune system response are discussed, a plausible role of polyomavirus-encoded and polyomavirus-induced microRNA in cancer is described, and the effect of Polyomaviruses on energy homeostasis and exosomes is explored. Therapeutic strategies against these emerging hallmarks of cancer are also suggested.

  • serological cross reactivity between human Polyomaviruses
    Reviews in Medical Virology, 2013
    Co-Authors: Ugo Moens, Marijke Van Ghelue, Xiaobo Song, Bernhard Ehlers
    Abstract:

    SUMMARY Until 2006, BKPyV and JCPyV were the only known human Polyomaviruses. A third polyomavirus, simian virus 40 whose natural host is the macaque was accidently introduced into man because of contaminated poliovirus vaccines, although there is epidemiological evidence that SV40 may be transmitted between man independently from contaminated vaccines. Since 2007, 10 new human Polyomaviruses have been identified: KIPyV, WUPyV, Merkel cell polyomavirus, trichodysplasia spinulosa-associated polyomavirus, and human Polyomaviruses 6, 7, 9, 10, STL, and 12. Moreover, the DNA of the monkey lymphotropic polyomavirus has been amplified from human peripheral blood. Seroepidemiological studies frequently based on the presence of antibodies against the major capsid protein VP1 or virus-like particles indicate that most human adults have been exposed to many, if not all, human Polyomaviruses. However, because of the high amino acid sequence identity between VP1 of some human Polyomaviruses, cross-reactivity of antibodies is occasionally observed. In addition, human sera possess reactivity against VP1 of Polyomaviruses from other species, suggesting serological cross-reaction with known or closely related, yet unidentified human Polyomaviruses and/or the possibility of zoonotic transmission. Thus, current serological results should be interpreted with caution, and controls excluding cross-reactivity with other Polyomaviruses are required. Copyright © 2013 John Wiley & Sons, Ltd.

  • genome analysis of the new human Polyomaviruses
    Reviews in Medical Virology, 2012
    Co-Authors: Marijke Van Ghelue, Bernhard Ehlers, Mahmud Tareq Hassan Khan, Ugo Moens
    Abstract:

    SUMMARY Polyomaviridae is a growing family of naked, double-stranded DNA viruses that infect birds and mammals. The last few years, several new members infecting birds or primates have been discovered, including seven human Polyomaviruses: KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. In addition, DNA and antibodies against the monkey lymphotropic polyomavirus have been detected in humans, indicating that this virus can also infect man. However, little is known about the route of infection, transmission, cell tropism, and, with the exception of Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus, the pathogenicity of these viruses. This review compares the genomes of these emerging human Polyomaviruses with previously known Polyomaviruses detected in man, reports mutations in different isolates, and predicts structural and functional properties of their viral proteins. Copyright © 2012 John Wiley & Sons, Ltd.

Mauro Tognon - One of the best experts on this subject based on the ideXlab platform.

  • age specific seroprevalences of merkel cell polyomavirus human Polyomaviruses 6 7 and 9 and trichodysplasia spinulosa associated polyomavirus
    Clinical and Vaccine Immunology, 2013
    Co-Authors: Jérôme T. J. Nicol, Remy Robinot, Giovanni Carandina, Antoine Touzé, Elisa Mazzoni, Audrey Carpentier, Mauro Tognon, Pierre Coursaget
    Abstract:

    Six new human Polyomaviruses have been identified since 2008 (Merkel cell polyomavirus [MCPyV], human polyomavirus 6 [HPyV6], HPyV7, HPyV9, trichodysplasia spinulosa polyomavirus [TSPyV], and Malawi polyomavirus [MWPyV]). The presence of specific antibodies against MCPyV, HPyV6, HPyV7, HPyV9, and TSPyV in 828 Italian subjects aged 1 to 100 years was investigated by virus-like particle-based enzyme-linked immunosorbent assays (ELISAs). The findings indicate that all of these new Polyomaviruses circulate widely in humans, with seroprevalences in adulthood ranging from 39.4% for HPyV9 to 87.1% for MCPyV, and that primary exposure is most intense in childhood, with the exception of HPyV7 and HPyV9, for which the seroprevalence increased throughout life. The proportion of subjects with high antibody titers was found to increase with age for MCPyV and to decrease with age for TSPyV.

  • age specific seroprevalences of merkel cell polyomavirus human Polyomaviruses 6 7 and 9 and trichodysplasia spinulosa associated polyomavirus
    Clinical and Vaccine Immunology, 2013
    Co-Authors: Jérôme T. J. Nicol, Remy Robinot, Giovanni Carandina, Antoine Touzé, Elisa Mazzoni, Audrey Carpentier, Mauro Tognon, Pierre Coursaget
    Abstract:

    Six new human Polyomaviruses have been identified since 2008 (Merkel cell polyomavirus [MCPyV], human polyomavirus 6 [HPyV6], HPyV7, HPyV9, trichodysplasia spinulosa polyomavirus [TSPyV], and Malawi polyomavirus [MWPyV]). The presence of specific antibodies against MCPyV, HPyV6, HPyV7, HPyV9, and TSPyV in 828 Italian subjects aged 1 to 100 years was investigated by virus-like particle-based enzyme-linked immunosorbent assays (ELISAs). The findings indicate that all of these new Polyomaviruses circulate widely in humans, with seroprevalences in adulthood ranging from 39.4% for HPyV9 to 87.1% for MCPyV, and that primary exposure is most intense in childhood, with the exception of HPyV7 and HPyV9, for which the seroprevalence increased throughout life. The proportion of subjects with high antibody titers was found to increase with age for MCPyV and to decrease with age for TSPyV.

  • bk virus jc virus and simian virus 40 infection in humans and association with human tumors
    Advances in Experimental Medicine and Biology, 2006
    Co-Authors: Giuseppe Barbantibrodano, Silvia Sabbioni, Fernanda Martini, Massimo Negrini, Alfredo Corallini, Mauro Tognon
    Abstract:

    BK virus (BKV), JC virus (JCV) and Simian Virus 40 (SV40) are Polyomaviruses, highly homologous at the DNA and protein levels. While the human Polyomaviruses BKV and JCV are ubiquitous in humans, SV40 is a simian virus which was introduced in the human population, between 1955 and 1963, by contaminated poliovaccines produced in SV40-infected monkey cells. Alternatively, SV40 or an SV40-like virus may have entered the human population before anti-poliovirus vaccination. Epidemiological evidence suggests that SV40 is now contagiously transmitted in the human population by horizontal infection, independently from the earlier contaminated poliovaccines. All three Polyomaviruses transform rodent and human cells and are oncogenic in rodents. JCV induces tumors also in experimentally inoculated monkeys. Transformation and oncogenicity induced by BKV, JCV and SV40 are due to the two viral oncoproteins, the large T antigen (Tag) and the small t antigen (tag), encoded in the early region of the viral genome. Both proteins display several functions. The large Tag acts mainly by blocking the functions of p53 and pRB family tumor suppressor proteins and by inducing in host cells chromosomal aberrations and instability. The principal effect of small tag is to bind the catalytic and regulatory subunits of the protein phosphatase PP2A, thereby constitutively activating the β-catenin pathway which drives cells into proliferation. All three Polyomaviruses are associated with specific human tumor types which correspond to the tumors induced by experimental inoculation of the three viruses in rodents and to the neoplasms arising in mice transgenic for the polyomavirus early region gene directed by the native viral early promoter-enhancer. Human tumors associated with BKV. JCV and SV40 contain viral DNA, generally episomic, express viral RNA and are positive for large Tag by immunohistochemistry. The low copy number of viral genomes in human tumors suggests that Polyomaviruses may transform human cells by a “hit and run” mechanism. An autocrine-paracrine effect, involving secretion of growth factors by cells expressing polyomavirus Tag, may be responsible for recruiting to proliferation Tag-negative cells in polyomavirus-associated human tumors.

Pierre Coursaget - One of the best experts on this subject based on the ideXlab platform.