4.6 Article

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

Journal

MOLECULAR NEUROBIOLOGY
Volume 56, Issue 7, Pages 4708-4717

Publisher

SPRINGER
DOI: 10.1007/s12035-018-1417-x

Keywords

Zika virus; Brain diseases; Human mesenchymal stem cells; Proteome; Microcephaly

Categories

Funding

  1. Brazilian funding agency Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES)
  2. Brazilian funding agency FAPERGS
  3. Brazilian funding agency Edital MCTIC/FNDCT-CNPq/MEC-CAPES/MS-Decit [14/2016, 440763/2016-9]
  4. NIH grants [NIH/NIHGM P41 GM103533-22, NIH/NIMH 5 R01 MH067880-14]

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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.

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