Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer

Abstract

As their name indicates, polyomaviruses (PyVs) can induce tumors. Mouse PyV, hamster PyV and raccoon PyV have been shown to cause tumors in their natural host. During the last 30 years, 15 PyVs have been isolated from humans. From these, Merkel cell PyV is classified as a Group 2A carcinogenic pathogen (probably carcinogenic to humans), whereas BKPyV and JCPyV are class 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer. Although the other PyVs recently detected in humans (referred to here as novel HPyV; nHPyV) share many common features with PyVs, including the viral oncoproteins large tumor antigen and small tumor antigen, as their role in cancer is questioned. This review discusses whether the nHPyVs may play a role in cancer based on predicted and experimentally proven functions of their early proteins in oncogenic processes. The functional domains that mediate the oncogenic properties of early proteins of known PyVs, that can cause cancer in their natural host or animal models, have been well characterized and we examined whether these functional domains are conserved in the early proteins of the nHPyVs and presented experimental evidence that these conserved domains are functional. Furthermore, we reviewed the literature describing the detection of nHPyV in human tumors.

MicroRNA dysregulations in Merkel cell carcinoma: Molecular mechanisms and clinical applications

“…Similarly, sT is implicated in cell transformation and survival, as it promotes oncogene activation 10 . Viral DNA integration induces deletions into the viral genome, leading to the generation of different truncated LT (tLT) forms which drive neoplastic transformation 11 . MCCN presents a high mutation rate caused by UV radiation‐induced DNA damages 12 .…”

“…10 Viral DNA integration induces deletions into the viral genome, leading to the generation of different truncated LT (tLT) forms which drive neoplastic transformation. 11 MCCN presents a high mutation rate caused by UV radiationinduced DNA damages. 12 The average number of MCCN mutations is ~1100 somatic single nucleotide variants/exome, with the frequent downregulation of RB1 and tumor protein p53 (TP53) (HGNC:11998) genes.…”

Human Oncogenic Viruses: Characteristics and Prevention Strategies—Lessons Learned from Human Papillomaviruses

“…Cellular tropism, genome organization and the associated neoplasia of both human DNA and RNA oncogenic viruses included in Group 1 are summarised in Table 1. Although animal polyomaviruses (PyVs) can cause tumours in their natural hosts or in animal models, the role of HPyVs in human cancer is still under investigation since cancer mainly arises in immunocompromised hosts [27,28]. The Merkel cell polyomavirus (MCPyV) is a naked double-stranded DNA virus with a small genome (5.4 kb), which replicates in epidermal keratinocytes and dermal fibroblasts.…”

Merkel Cell Polyomavirus: Infection, Genome, Transcripts and Its Role in Development of Merkel Cell Carcinoma

“…This substance was believed to be a virus and was later referred to as "SE polyomavirus" [3,4]. Similarly, hamster and raccoon polyomavirus can cause tumors in their natural hosts [5], and this potential to trigger multiple tumors in mice and hamsters led to the name polyomaviridae ("poly" for many and "oma" for tumors) for the respective family. Since these early days, 117 polyomavirus species have been identified, which according to the virus taxonomy 2021 release, are grouped into eight genera (online available at https://ictv.global/taxonomy/ accessed on 9 January 2023).…”