Pathogens (Nov 2022)

Molecular Mimicry Analyses Unveiled the Human Herpes Simplex and Poxvirus Epitopes as Possible Candidates to Incite Autoimmunity

  • Sara Begum,
  • Sara Aiman,
  • Shujaat Ahmad,
  • Abdus Samad,
  • Mazen Almehmadi,
  • Mamdouh Allahyani,
  • Abdulelah Aljuaid,
  • Sahib Gul Afridi,
  • Asifullah Khan

DOI
https://doi.org/10.3390/pathogens11111362
Journal volume & issue
Vol. 11, no. 11
p. 1362

Abstract

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Clinical epidemiological studies have reported that viral infections cause autoimmune pathology in humans. Host-pathogen protein sequences and structure-based molecular mimicry cause autoreactive T cells to cross-activate. The aim of the current study was to implement immunoinformatics approaches to infer sequence- and structure-based molecular mimicry between viral and human proteomic datasets. The protein sequences of all the so far known human-infecting viruses were obtained from the VIPR database, and complete human proteome data were retrieved from the NCBI repository. Based on a predefined, stringent threshold of comparative sequence analyses, 24 viral proteins were identified with significant sequence similarity to human proteins. PathDIP identified the enrichment of these homologous proteins in nine metabolic pathways with a p-value 50 < 50 nM. Downstream molecular docking analyses identified that lead virus-human homologous epitopes feasibly interact with HLA and TLR4 types of immune receptors. The vast majority of these top-hit homolog epitopic peptides belong to the herpes simplex and poxvirus families. These lead epitope biological sequences and 3D structural-based molecular mimicry may be promising for interpreting herpes simplex virus and poxvirus infection-mediated autoimmune disorders in humans.

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