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Molecular Neurobiology

, Volume 56, Issue 7, pp 4708–4717 | Cite as

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

  • Walter O. Beys-da-SilvaEmail author
  • Rafael L. Rosa
  • Lucélia Santi
  • Markus Berger
  • Sung Kyu Park
  • Alexandre R. Campos
  • Paula Terraciano
  • Ana Paula M. Varela
  • Thais F. Teixeira
  • Paulo M. Roehe
  • André Quincozes-Santos
  • John R. YatesIII
  • Diogo O. Souza
  • Elizabeth O. Cirne-Lima
  • Jorge A. GuimarãesEmail author
Article

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

Zika virus Brain diseases Human mesenchymal stem cells Proteome Microcephaly 

Notes

Acknowledgements

The authors would like to thank Dr. E. Durigon, ICB/USP, for supplying the ZIKV strain. PMR is a 1A CNPq research fellow. APMV and TFT acknowledges postdoctoral fellowship support by CNPq/HCPA.

Funding Information

This work was supported by the Brazilian funding agencies Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES), FAPERGS, Edital MCTIC/FNDCT-CNPq/ MEC-CAPES/ MS-Decit / No 14/2016, project 440763/2016-9. The study was also supported by NIH grants NIH/NIHGM P41 GM103533-22 and NIH/NIMH 5 R01 MH067880-14 (to JRY).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was approved by the institutional research ethics committee of Hospital de Clínicas de Porto Alegre (Federal University of Rio Grande do Sul) under protocol # 2018-0059.

Supplementary material

12035_2018_1417_MOESM1_ESM.pdf (122 kb)
ESM 1 (PDF 121 kb)
12035_2018_1417_MOESM2_ESM.pdf (58 kb)
Supplementary Figure 1 PI3K-AKT signaling pathway affected by ZIKV infection in hMSC. Green rectangle: protein down-regulated in ZIKV infection. (PDF 58 kb)
12035_2018_1417_MOESM3_ESM.pdf (41 kb)
Supplementary Figure 2 mTOR signaling pathway affected by ZIKV infection in hMSC. Green rectangle: proteins down-regulated in ZIKV infection; red rectangle: protein up-regulated in ZIKV infection. (PDF 40 kb)
12035_2018_1417_MOESM4_ESM.pdf (178 kb)
Supplementary Figure 3 Phosphatidylinositol signaling system affected by ZIKV infection in hMSC. Green rectangle: proteins down-regulated in ZIKV infection. (PDF 177 kb)
12035_2018_1417_MOESM5_ESM.docx (13 kb)
Supplementary Table 1 (DOCX 13 kb)
12035_2018_1417_MOESM6_ESM.xlsx (160 kb)
Supplementary Table 2 (XLSX 159 kb)
12035_2018_1417_MOESM7_ESM.docx (27 kb)
Supplementary Table 3 (DOCX 26 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Walter O. Beys-da-Silva
    • 1
    • 2
    Email author
  • Rafael L. Rosa
    • 2
    • 3
  • Lucélia Santi
    • 1
    • 2
  • Markus Berger
    • 2
  • Sung Kyu Park
    • 4
  • Alexandre R. Campos
    • 5
  • Paula Terraciano
    • 2
  • Ana Paula M. Varela
    • 6
  • Thais F. Teixeira
    • 6
  • Paulo M. Roehe
    • 7
  • André Quincozes-Santos
    • 8
  • John R. YatesIII
    • 4
  • Diogo O. Souza
    • 8
  • Elizabeth O. Cirne-Lima
    • 2
    • 9
    • 10
  • Jorge A. Guimarães
    • 2
    • 3
    Email author
  1. 1.Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Centro de Pesquisa ExperimentalHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Biologia Celular e MolecularUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Department of Chemical PhysiologyThe Scripps Research InstituteLa JollaUSA
  5. 5.Proteomics CoreSanford Burnham Prebys Medical Discovery InstituteLa JollaUSA
  6. 6.Centro de Cardiologia ExperimentalInstituto de Cardiologia/Fundação Universitária de CardiologiaPorto AlegreBrazil
  7. 7.Departamento de MicrobiologiaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  8. 8.Departamento de BioquímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  9. 9.Programa de Pós-Graduação em Ginecologia e ObstetríciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  10. 10.Departamento de Patologia Clínica Veterinária, Faculdade de VeterináriaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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