4.6 Review

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

Journal

FRONTIERS IN MICROBIOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2022.834368

Keywords

DDR; DnaJ; PP2A; p53; retinoblastoma; seroprevalence; signaling pathways

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Polyomaviruses can induce tumors, with some strains classified as carcinogenic to humans and others possibly carcinogenic. Whether novel HPyVs play a role in cancer is still under question, as they share common features with known PyVs but their role in oncogenic processes is not fully understood. Studies have examined the functional domains of early proteins in novel HPyVs and presented experimental evidence of their potential oncogenic properties. Detection of novel HPyV in human tumors has also been reviewed in the literature.
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.

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