Zika Virus Infection of Human Mesenchymal Stem Cells Promotes Differential Expression of Proteins Linked to Several Neurological Diseases
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Updated: Feb 3, 2026

Zika Virus Infection of Cultured Human Fetal Brain Neural Stem Cells for Immunocytochemical Analysis
Published on: February 5, 2018
Walter O Beys-da-Silva1,2, Rafael L Rosa3,4, Lucélia Santi5,3
1Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. walter.beys@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.
Insights
Zika virus (ZIKV) infection in human cells alters metabolism and key cellular processes. This study reveals potential links between ZIKV and neurodegenerative diseases beyond microcephaly.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- The Zika virus (ZIKV) outbreak in Brazil has been linked to microcephaly.
- The full spectrum of ZIKV-induced cellular damage and associated neurological complications remains unclear.
Purpose of the Study:
- To investigate the proteomic changes in human mesenchymal stem cells (hMSC) upon infection with a Brazilian ZIKV strain.
- To identify potential molecular mechanisms and associated neuropathologies linked to ZIKV infection.
Main Methods:
- Differential proteome analysis using shotgun proteomics (MudPIT).
- Analysis of human mesenchymal stem cells (hMSC) infected with ZIKV.
Main Results:
- ZIKV infection reprogrammed nucleotide metabolism and energy production pathways (glycolysis).
- ZIKV potentially inhibited autophagy, neurogenesis, and immune responses via signaling pathway downregulation.
- Altered expression of proteins associated with Alzheimer's, autism, ALS, and Parkinson's diseases was observed in ZIKV-infected hMSC.
Conclusions:
- ZIKV infection significantly impacts cellular metabolism and function in hMSC.
- This study presents novel evidence linking ZIKV infection to proteins implicated in various neurodegenerative and developmental disorders, extending beyond microcephaly.
- Findings suggest ZIKV may have broader neurological implications requiring further investigation.
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