Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases

Mol Neurobiol. 2019 Jul;56(7):4708-4717. doi: 10.1007/s12035-018-1417-x. Epub 2018 Oct 30.

Abstract

The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer's disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson's disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.

Keywords: Brain diseases; Human mesenchymal stem cells; Microcephaly; Proteome; Zika virus.

MeSH terms

  • Adult
  • Female
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Nervous System Diseases / pathology*
  • Nervous System Diseases / virology*
  • Proteome / metabolism
  • Zika Virus / physiology*
  • Zika Virus Infection / metabolism*
  • Zika Virus Infection / pathology*

Substances

  • Proteome