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Review
. 2020 Oct 12;12(10):1156.
doi: 10.3390/v12101156.

JCPyV VP1 Mutations in Progressive MultifocalLeukoencephalopathy: Altering Tropismor Mediating Immune Evasion?

Matthew D Lauver  1 , Aron E Lukacher  1
Affiliations
Review

JCPyV VP1 Mutations in Progressive MultifocalLeukoencephalopathy: Altering Tropismor Mediating Immune Evasion?

Matthew D Lauver et al. Viruses. .

Abstract

Polyomaviruses are ubiquitous human pathogens that cause lifelong, asymptomatic infections in healthy individuals. Although these viruses are restrained by an intact immune system, immunocompromised individuals are at risk for developing severe diseases driven by resurgent viral replication. In particular, loss of immune control over JC polyomavirus can lead to the development of the demyelinating brain disease progressive multifocal leukoencephalopathy (PML). Viral isolates from PML patients frequently carry point mutations in the major capsid protein, VP1, which mediates virion binding to cellular glycan receptors. Because polyomaviruses are non-enveloped, VP1 is also the target of the host's neutralizing antibody response. Thus, VP1 mutations could affect tropism and/or recognition by polyomavirus-specific antibodies. How these mutations predispose susceptible individuals to PML and other JCPyV-associated CNS diseases remains to be fully elucidated. Here, we review the current understanding of polyomavirus capsid mutations and their effects on viral tropism, immune evasion, and virulence.

Keywords: JCPyV; MuPyV; Progressive multifocal leukoencephalopathy (PML); VP1; antibody escape; persistent infection; polyomavirus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solvent-exposed loops and β strands of JCPyV VP1. The exterior surface of VP1 is formed by the BC, DE, EF, and HI loops (shades of purple) connecting two sets of antiparallel β strands, BIDG and CHEF (shades of red and blue). Figure generated in UCSF Chimera using JCPyV VP1 structure 3NXG [18,22].
Figure 2
Figure 2
Overlap of receptor binding residues and locations of JCPyV-PML VP1 mutations. Side chains of VP1 amino acids that interact with LSTc are shown in yellow. Sites of JCPyV-PML VP1 mutations are shown in red. Residues that are both involved in LSTc binding and mutated in PML are shown in orange. LSTc interacting residues are assigned based on Neu et al. [18]. Indicated sites of PML mutations have been reported in several studies [76,84,85,101]. Neighboring VP1 subunits within the VP1 pentamer are denoted with shades of blue. Figure generated in UCSF Chimera using JCPyV VP1 structure 3NXG [18,22]. VP1 residue numbering throughout this article excludes the initial methionine.
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References

    1. Buck C.B., Doorslaer K.V., Peretti A., Geoghegan E.M., Tisza M.J., An P., Katz J.P., Pipas J.M., McBride A.A., Camus A.C., et al. The ancient evolutionary history of polyomaviruses. PLoS Pathog. 2016;12 doi: 10.1371/journal.ppat.1005574. - DOI - PMC - PubMed
    1. Gross L. A filterable agent, recovered from Ak leukemic extracts, causing salivary gland carcinomas in C3H mice. Proc. Soc. Exp. Biol. Med. 1953;83:414–421. doi: 10.3181/00379727-83-20376. - DOI - PubMed
    1. Lehn H., Müller H. Cloning and characterization of budgerigar fledgling disease virus, an avian polyomavirus. Virology. 1986;151:362–370. doi: 10.1016/0042-6822(86)90056-5. - DOI - PubMed
    1. Kamminga S., van der Meijden E., Feltkamp M.C.W., Zaaijer H.L. Seroprevalence of fourteen human polyomaviruses determined in blood donors. PLoS ONE. 2018;13:e0206273. doi: 10.1371/journal.pone.0206273. - DOI - PMC - PubMed
    1. Bofill-Mas S., Pina S., Girones R. Documenting the epidemiologic patterns of polyomaviruses in human populations by studying their presence in urban sewage. Appl. Environ. Microbiol. 2000;66:238–245. doi: 10.1128/AEM.66.1.238-245.2000. - DOI - PMC - PubMed

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