title: Zika virus and autoimmunity: From microcephaly to Guillain-Barré syndrome, and beyond.
abstract: Zika virus (ZIKV) infection during pregnancy may be linked to fetal neurological complications that include brain damage and microcephaly. How the viral infection relates to fetal brain malformations is unknown. This study analyzes ZIKV polyprotein for peptide sharing with human proteins that, when altered, associate with microcephaly and brain calcifications. Results highlight a vast viral versus human peptide commonality that, in particular, involves centriolar and centrosomal components canonically cataloged as microcephaly proteins, i.e., C2CD3, CASC5, CP131, GCP4, KIF2A, STIL, and TBG. Likewise, a search for ZIKV peptide occurrences in human proteins linked to Guillain-Barré-like syndromes also show a high, unexpected level of peptide sharing. Of note, further analyses using the Immune Epitope DataBase (IEDB) resource show that many of the shared peptides are endowed with immunological potential. The data indicate that immune reactions following ZIKV infection might be a considerable source of crossreactions with brain-specific proteins and might contribute to the ZIKV-associated neuropathologic sequelae.
authors.affiliation: Brain and Language Laboratory, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Lucchese
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70126 Bari, Italy.
authors.forename: Darja
authors.initials: D
authors.lastname: Kanduc
mesh_terms: D015551:Autoimmunity; D001921:Brain / Q000473:pathology; D003429:Cross Reactions; D005260:Female; D005315:Fetal Diseases / Q000473:pathology / Q000821:virology*; D020275:Guillain-Barre Syndrome / Q000473:pathology / Q000821:virology*; D006801:Humans; D008831:Microcephaly / Q000473:pathology / Q000821:virology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D010449:Peptide Mapping; D020815:Polyproteins / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000473:pathology* / Q000821:virology*
chemical_list: D009419:Nerve Tissue Proteins; D020815:Polyproteins; D014764:Viral Proteins
keywords: Aicardi-Goutieres syndromes; Autoimmunity; Brain calcification; Centriolar and centrosomal proteins; Crossreactivity; Guillain-Barré-like syndromes; Microcephaly; Ocular anomalies; Peptide sharing; Zika virus infection