2. Academic Validation
  3. EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

  • Virology. 2020 Jan 2;539:121-128. doi: 10.1016/j.virol.2019.10.016.
Bibha Dahal 1,  Shih-Chao Lin 1,  Brian D Carey 1,  Jonathan L Jacobs 2,  Jonathan D Dinman 3,  Monique L van Hoek 1,  Andre A Adams 4,  Kylene Kehn-Hall 5
Affiliations

Affiliations

  • 1 National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, USA.
  • 2 QIAGEN Bioinformatics, Aarhus, Denmark; QIAGEN Bioinformatics, Maryland, USA.
  • 3 Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.
  • 4 Naval Research Laboratory, Washington, DC, USA.
  • 5 National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, USA. Electronic address: kkehnhal@gmu.edu.
PMID: 31733451 DOI: 10.1016/j.virol.2019.10.016
Abstract

Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post Infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced Apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced Apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.

Keywords

Alphavirus; Apoptosis; EGR1; ERK; Early growth response 1; PERK; UPR; Unfolded protein response; VEEV; Venezuelan equine encephalitis virus.

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