Molecular mimicry as a mechanism of viral immune evasion and autoimmunity
Cole Maguire, Chumeng Wang, Akshara Ramasamy, Cara Fonken, Brinkley Morse, Nathan Lopez, Dennis Wylie, Esther Melamed
Abstract
Mimicry of host protein structures, or ‘molecular mimicry’, is a common mechanism employed by viruses to evade the host’s immune system. Short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T cells from the host, but the prevalence of such mimics throughout the human virome has not been fully explored. Here we evaluate 134 human-infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the Herpesviridae and Poxviridae families. Furthermore, host proteins related to cellular replication and inflammation, autosomes, the X chromosome, and thymic cells are enriched as viral mimicry targets. Finally, we find that short linear mimicry from Epstein-Barr virus (EBV) is higher in auto-antibodies found in patients with multiple sclerosis than previously appreciated. Our results thus hint that human-infecting viruses leverage mimicry in the course of their infection, and that such mimicry may contribute to autoimmunity, thereby prompting potential targets for therapies. Viruses often evolve molecular mimicry with host proteins for immune evasion. Here the authors assess short linear mimicry of 134 viruses to find abundance of such mimicry in herpes and pox viruses, while overlaps between Epstein-Barr virus antigens and auto-antibodies from patients with multiple sclerosis hints at a crosstalk between viral infection and autoimmunity.