Dysregulation of RNA editing may help explain pathogenicity mechanisms of congenital Zika syndrome and Guillain-Barre syndrome

Abstract

Many Zika virus (ZIKV) pathogenesis-related studies have focused primarily on virus-driven pathology and neurotoxicity, instead of considering the possibility of pathogenesis as an (unintended) consequence of host innate immunity: specifically, as the side-effect of an otherwise well-functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post-transcriptional RNA editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. We collect and synthesize existing evidence of ZIKV-mediated changes in expression of adenosine deaminases that act on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for potential translational applications, including genomic profile-based molecular diagnostic tools and/or treatment strategies.