Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus

Sathya N. Thulasi Raman, Elyse Latreille, Jun Gao, Wanyue Zhang, Jianguo Wu, Marsha S. Russell, Lisa Walrond, Terry Cyr, Jessie R. Lavoie, David Safronetz, Jingxin Cao, Simon Sauve, Aaron Farnsworth, Wangxue Chen, Pei Yong Shi, Youchun Wang, Lisheng Wang, Michael Rosu-Myles, Xuguang Li

Research output: Contribution to journalArticle

Abstract

Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.

Original languageEnglish (US)
Pages (from-to)2046-2060
Number of pages15
JournalEmerging Microbes and Infections
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Ephrin signaling
  • ingenuity pathway analysis
  • Neural progenitor cells
  • PPAR signaling
  • proteomics
  • ZIKV

ASJC Scopus subject areas

  • Parasitology
  • Epidemiology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Virology
  • Infectious Diseases

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  • Cite this

    Thulasi Raman, S. N., Latreille, E., Gao, J., Zhang, W., Wu, J., Russell, M. S., Walrond, L., Cyr, T., Lavoie, J. R., Safronetz, D., Cao, J., Sauve, S., Farnsworth, A., Chen, W., Shi, P. Y., Wang, Y., Wang, L., Rosu-Myles, M., & Li, X. (2020). Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus. Emerging Microbes and Infections, 9(1), 2046-2060. https://doi.org/10.1080/22221751.2020.1818631