open access publication

Article, 2019

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

Virology, ISSN 0042-6822, 1096-0341, Volume 539, Pages 121-128, 10.1016/j.virol.2019.10.016

Contributors

Dahal, Bibha 0000-0001-8746-7954 [1] Lin, Shih-Chao 0000-0003-2942-5937 [1] Carey, Brian D 0000-0002-5493-3880 [1] Jacobs, Jonathan L 0000-0001-5608-4256 [2] [3] Dinman, Jonathan D 0000-0002-2402-9698 [4] Van Hoek, Monique Louise 0000-0003-1679-4899 [1] Adams, André A 0000-0002-2979-249X [5] Kehn-Hall, Kylene- 0000-0001-8036-7213 (Corresponding author) [1]

Affiliations

  1. [1] George Mason University
    2. [NORA names: United States; America, North; OECD];
  2. [2] Qiagen (Denmark)
    3. [NORA names: Qiagen; Private Research; Denmark; Europe, EU; Nordic; OECD];
  3. [3] Qiagen (United States)
    4. [NORA names: United States; America, North; OECD];
  4. [4] University of Maryland, College Park
    5. [NORA names: United States; America, North; OECD];
  5. [5] United States Naval Research Laboratory
    6. [NORA names: United States; America, North; OECD]

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

EGR1 gene expression, EGR1 induction, ERK, ERK1/2, MAPK, PI3, PI3K, Venezuelan equine encephalitis virus, Venezuelan equine encephalitis virus infection, activity, apoptosis, astrocytes, cell death, cell survival, cells, data, death, disease, early growth response 1, encephalitis virus, endoplasmic reticulum kinase, equine, equine encephalitis virus, expression, extracellular signal-regulated kinase1/2, gene expression, genes, growth response 1, human primary astrocytes, humans, impact, impact viral replication, increased cell survival, induction, infection, kinase, kinase1/2, knockdown, knockdown of EGR1, knockdown of ERK1/2, mitogen, neurotropic viruses, p38, p38 mitogen, pathway, phosphoinositide, phosphoinositide 3-kinase, post, post-infection, primary astrocytes, protein, protein kinase R (PKR)-like endoplasmic reticulum kinase, reduced viral replication, replication, rescue cells, response 1, signal, signaling pathways regulating cell death, survival, upregulation, viral replication, virus, virus infection

Funders

  • Defense Threat Reduction Agency
  • United States Department of the Navy

Data Provider: Digital Science

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+