Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

• Published in: BioEssays Vol. 41; no. 6; pp. e1800239 - n/a
• Main Authors: Piontkivska, Helen, Plonski, Noel‐Marie, Miyamoto, Michael M., Wayne, Marta L.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2019
• Subjects: Adenosine; Adenosine Deaminase - genetics; adenosine deaminases acting on RNA (ADAR) editing; Adult; Autophagy; Biomarkers; Cell proliferation; congenital Zika syndrome (CZS); Editing; Female; Gene Expression; Guillain-Barre Syndrome - pathology; Guillain-Barre Syndrome - virology; Guillain–Barré syndrome (GBS); Host-Pathogen Interactions - immunology; Humans; Immunity; Immunity, Innate; Infant; Infant, Newborn; Infants; Innate immunity; Microcephaly - virology; Neurotoxicity; Noninvasive Prenatal Testing; Pathogenesis; Pathogenicity; Pathogens; Phagocytosis; Pregnancy; RNA Editing; RNA-Binding Proteins - genetics; Signs and symptoms; Therapeutic applications; Transcription; Uterus; Vector-borne diseases; Viruses; Zika virus; Zika virus (ZIKV); Zika Virus - pathogenicity; Zika Virus Infection - pathology; Zika Virus Infection - virology; Zika virus (ZIKV); RNA editing; adenosine deaminases acting on RNA (ADAR) editing; innate immunity; congenital Zika syndrome (CZS); Guillain-Barré syndrome (GBS)
• ISSN: 0265-9247; 1521-1878; 1521-1878
• DOI: 10.1002/bies.201800239

Previous studies of Zika virus (ZIKV) pathogenesis have focused primarily on virus‐driven pathology and neurotoxicity, as well as host‐related changes in cell proliferation, autophagy, immunity, and uterine function. It is now hypothesized that ZIKV pathogenesis arises instead 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. The authors collect and synthesize existing evidence of ZIKV‐mediated changes in the expression of adenosine deaminases acting on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for future research directions, including potential treatment strategies. Adenosine deaminases acting on RNA (ADAR) enzymes are key regulators of messenger RNA (mRNA), and thus, protein diversity in humans. The authors outline how Zika virus infections can lead to ADAR editing dysregulation, and thereby, the neurodevelopmental and neurodegenerative pathologies of congenital Zika and Guillain–Barré syndromes, and how to test this hypothesis.