Viral Hijacking of Formins in Neurodevelopmental Pathologies

Trends Mol Med. 2017 Sep;23(9):778-785. doi: 10.1016/j.molmed.2017.07.004. Epub 2017 Aug 10.

Abstract

The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon fetal exposure. Significant progress has been made in our understanding of the interactions between ZIKV and the pregnant host, but there is still a critical need to understand how ZIKV and other neurotropic viruses affect fetal neurodevelopment. Diaphanous-related formins (Diaphs) have recently been identified as microcephaly-associated proteins in humans and mice. Mutations in Diaphs affect the function of neural progenitor cells, much like prenatal viral infection. We present a novel hypothesis that viruses 'hijack' Diaphs in neural progenitor cells, causing autonomous differentiation and apoptosis of neural progenitor cells, which could potentially contribute to virus-associated neurological pathologies.

Keywords: Zika; cytomegalovirus; diaphanous-related formins; microcephaly; neurodevelopment.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Disease Outbreaks*
  • Formins
  • Humans
  • Microcephaly* / epidemiology
  • Microcephaly* / genetics
  • Microcephaly* / metabolism
  • Microcephaly* / pathology
  • Neural Stem Cells* / metabolism
  • Neural Stem Cells* / pathology
  • Zika Virus Infection* / epidemiology
  • Zika Virus Infection* / genetics
  • Zika Virus Infection* / metabolism
  • Zika Virus Infection* / pathology
  • Zika Virus* / genetics
  • Zika Virus* / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DIAPH1 protein, human
  • Formins