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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Capsid / immunology
  • Capsid Proteins / genetics*
  • Capsid Proteins / immunology
  • Host Specificity / genetics
  • Humans
  • Immune Evasion / genetics*
  • Immune Evasion / immunology
  • JC Virus / genetics*
  • JC Virus / immunology*
  • Leukoencephalopathy, Progressive Multifocal / genetics
  • Leukoencephalopathy, Progressive Multifocal / immunology*
  • Leukoencephalopathy, Progressive Multifocal / virology
  • Mice
  • Mutation
  • Viral Tropism / genetics
  • Virus Replication / genetics

Substances

  • Capsid Proteins
  • VP1 protein, polyomavirus