PT - JOURNAL ARTICLE AU - E. Jane Homan AU - Robert W. Malone AU - Steven J. Darnell AU - Robert D Bremel TI - Antibody mediated epitope mimicry in the pathogenesis of Zika virus related disease AID - 10.1101/044834 DP - 2016 Jan 01 TA - bioRxiv PG - 044834 4099 - http://biorxiv.org/content/early/2016/03/19/044834.short 4100 - http://biorxiv.org/content/early/2016/03/19/044834.full AB - The association of Guillain-Barré syndrome with Zika virus infection raises suspicion of autoimmunity in the pathogenesis of Zika associated disease. Using computational analysis to identify predicted B and T cell epitopes, we assessed whether antibodies elicited by B cell epitopes in Zika virus may also target B cell epitopes in the human proteome. We detected amino acid motifs predicted to be B cell epitopes in Zika virus proteins which are also present in human proteins, including pro-neuropeptide Y (proNPY), NAV2 and other proteins with interacting neurophysiologic function. We examine the predicted MHC binding of peptides likely to provide T cell help to the potential mimic epitopes. Some potential mimic epitopes in Zika virus envelope have apparently strong T cell help, likely facilitating immunoglobulin class switch. We also identify epitope mimic commonalities with dengue serotypes 1 and 3. We hypothesize that antibodies to Zika virus epitopes may contribute to the pathogenesis of Zika-associated Guillain-Barré syndrome, microcephaly, and ocular lesions, and may be a driver of autoimmunity. The risk associated with responses to potential epitope mimics must be addressed in the development of vaccines and therapeutics for Zika virus infections.Author Summary Using computational immunologic analysis, we examine the possibility that anti-Zika antibodies are binding to mimic epitopes on human proteins and that this autoimmunity may be a driver for some of the clinical signs associated with Zika virus infection. These include Guillain Barré Syndrome, other neurophysiologic deficits, and the Zika Fetal Syndrome, including microcephaly. We identify specific proteins and epitopes to which anti-Zika antibodies may bind. The prospect that the pathogenesis of ZIKV may involve an antibody-mediated autoimmune component must be addressed in vaccine and therapeutic development.