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Review
. 2022 Feb 18:13:834368.
doi: 10.3389/fmicb.2022.834368. eCollection 2022.

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

Ugo Moens  1 , Carla Prezioso  2   3 , Valeria Pietropaolo  3
Affiliations
Review

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

Ugo Moens et al. Front Microbiol. .

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.

Keywords: DDR; DnaJ; PP2A; p53; retinoblastoma; seroprevalence; signaling pathways.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Functional domains in the LT-ags of HPyVs. The amino acid sequence of the functional domains is given in the corresponding colored box. The consensus sequence (Con) for each domain is shown. M = MPyV (J02288), Ha = HaPyV (NC_001663), SV = SV40 (NC_001669), BK = BKPyV (NC_001538), JC = JCPyV (NC_001699), KI = KIPyV (NC_009238), WU = WUPyV (NC_009539), MC = MCPyV (NC_010277), H6 = HPyV6 (NC_014406), H7 = HPyV7 (NC_014407), TS = TSPyV (NC_014361), H9 = HPyV9 (NC_015150), H10 = HPyV10 (JX262162), STL = STLPyV (NC_020890), H12 = HPyV12 (NC_024118), NJ = NJPyV-2013 (NC_024118), LI = LIPyV (NC_034253), and Q = QPyV (BK010702. The accession number is given in parenthesis. CR1 = conserved region 1.
FIGURE 2
FIGURE 2
Functional domains in the sT-ags of HPyVs. The amino acid sequence of the functional domains is given in the corresponding colored box. See legend Figure 1 for details.
FIGURE 3
FIGURE 3
Alternative early transcripts of TSPyV. Modified after (van der Meijden et al., 2015; van der Meijden and Feltkamp, 2018).
FIGURE 4
FIGURE 4
Amino acid sequence of MT-ag, ALT, sT-ag and LT-ag of TSPyV. The common sequences are enlightened in the same color. Putative functional motifs are shown.
See this image and copyright information in PMC

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