Oncogenic potentials of the human polyomavirus regulatory proteins

Abstract

The polyomaviruses BK, JC and SV40 are common in the human population. Their DNA genomes encode large T-antigen, small t-antigen, agnoprotein, and the capsid proteins VP1-3. Studies with these viruses have contributed extensively to the understanding of processes such as replication, transcriptional and posttranscriptional regulation, and cell cycle control. All three viruses can transform human cells in vitro, can induce tumours in animal models, and are strongly association with certain human cancers. It is generally assumed that large T-antigen is the major protein involved in neoplastic processes and that large T-antigen predominantly exerts its effect through deregulation of the tumour suppressors p53 and the retinoblastoma family members. However, additional properties of large T-antigen as well as the other viral proteins contribute to oncogenic processes. This review presents the different mechanisms by which the polyomavirus proteins can induce transformation and discusses which mechanisms may be operational in polyomavirus-positive cancers.

Presence and role of Simian Virus 40 (SV40) in malignant pleural mesothelioma

“…The strong affinity of Tag for binding and inactivating p53 results in the cell avoiding key cell cycle checkpoints, thus surviving the otherwise fatal DNA damage and undergoing mitosis. 24,25 By escaping apoptosis and surviving, asbestos-damaged SV40 infected mesothelial cells pave the way to malignant transformation. It is very likely that asbestos fibres and viral Tag and tag interact and synergistically activate cellular signalling pathways, especially the ERK/ AP-1 pathway, that lead to cell proliferation, malignant transformation and invasion.…”

Molecular pathological findings of Merkel cell polyomavirus in lung cancer: A possible etiopathogenetic link?

“…2 The aforementioned viruses BKV, JCV and SV40, or their early proteins can induce tumors in animal models, and can immortalize or transform cultured cells, including human cells. 4,12 However, similar studies on the newly discovered polyoma viruses are lacking.…”

“…Recently, the interplay of the microenvironment, pathogens, immunity, inflammation, cellular epigenetic alterations and various chronic diseases has attracted increasing attention. [12][13][14] Previous studies thus far have shown that factors, such as disease stage, clinical parameters and methodological issues are rather minor issues. It is becoming more evident that further studies are required to determine whether polyomavirus may be placed among the determinants of risk.…”

Large T antigen variants of human polyomaviruses 9 and 12 and seroreactivity against their N terminus

“…The early proteins have regulatory functions, and a small number of mammalian PyVs have been reported to be tumorigenic in their natural host. Although 13 distinct human polyomaviruses have at present been discovered and the oncogenic properties of the human BK polyomavirus (BKPyV), JC polyomavirus (JCPyV) and the Merkel cell polyomavirus (MCPyV) in vitro and in animal models have been documented by numerous reports (reviewed in [2][3][4][5]), MCPyV is presently the only human virus that seems to be associated with human cancer (Merkel cell carcinoma, MCC) [6] (reviewed in [7]). BKPyV and JCPyV have also been linked to cancer development but this issue remains controversial and largely unresolved (reviewed in [8][9][10][11]).…”

“…In addition, murine PyV (MPyV) [16,17], hamster PyV (HaPyV) [18] and simian virus 40 (SV40) [19] induce tumours in laboratory animals under experimental conditions. Large T antigen (LTAg) and small T antigen (STAg) are known to play an essential role in viral transcription and replication [2,[20][21][22]. LTAg drives the infected cell into S phase status, the condition for optimal viral replication, and recruits cellular replication factors for promoting viral DNA replication via its helicase domain [22,23].…”