A possible role for autoimmunity through molecular mimicry in alphavirus mediated arthritis

Sci Rep. 2020 Jan 22;10(1):938. doi: 10.1038/s41598-019-55730-6.

Abstract

Alphaviral infections are foremost in causing debilitating clinical outcomes in humans characterized by rheumatic arthritis like conditions. Though the presence of virus in joints and associated inflammation has been implicated as one of the reasons for the acute and chronic polyarthritis post alphaviral infections, the basis for rheumatic like outcomes is not clear. Through an in silico analysis, we have investigated the possibility of an autoimmune process mediated through molecular mimicry in alphaviral infection induced pathogenicity. Interestingly, sequence alignment of the structural polyproteins belonging to arthritogenic alphaviruses revealed conserved regions which share homology with human proteins implicated in rheumatoid arthritis (RA). These conserved regions were predicted to exhibit binding to HLA class II alleles, showcasing their potential to incite T cell help. Molecular docking of the viral peptide and the corresponding homologous region in the human protein onto HLA-DRB1 revealed strong similarities in their binding patterns. Linear and conformational B cell epitope prediction analyses showed that these potential mimics have high propensity to elicit an efficient B cell response. We thus propose that the origin of polyarthritis post-arthritogenic alphaviral infections may also be mediated through a hitherto unknown autoimmune response due to the presence of cross-reactive epitopes between viral and human proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alphavirus / pathogenicity*
  • Alphavirus Infections*
  • Arthritis / immunology*
  • Arthritis / virology*
  • Autoimmunity*
  • B-Lymphocytes / immunology
  • Epitopes
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Molecular Mimicry / immunology*
  • T-Lymphocytes / immunology
  • Viral Proteins / genetics

Substances

  • Epitopes
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II
  • Viral Proteins