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Mol Neurobiol. 2018 Oct 30. doi: 10.1007/s12035-018-1417-x. [Epub ahead of print]

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

Author information

1
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. walter.beys@ufrgs.br.
2
Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. walter.beys@ufrgs.br.
3
Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
4
Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
5
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
6
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
7
Proteomics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
8
Centro de Cardiologia Experimental, Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil.
9
Departamento de Microbiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
10
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
11
Programa de Pós-Graduação em Ginecologia e Obstetrícia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
12
Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
13
Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. guimar@cbiot.ufrgs.br.
14
Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. guimar@cbiot.ufrgs.br.

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

PMID:
30377986
DOI:
10.1007/s12035-018-1417-x

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