AI Article Synopsis
- Venezuelan equine encephalitis virus (VEEV) infects human primary astrocytes, leading to significant disease and cell death.
- The virus triggers an increase in early growth response 1 (EGR1) gene expression, which is influenced by specific signaling pathways (ERK1/2 and PERK), but not others like p38 MAPK or PI3K.
- Reducing EGR1 levels lessens apoptosis and viral replication, while inhibiting ERK1/2 or PERK boosts cell survival and reduces viral effects, showing the critical role these pathways play in VEEV infection.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126400 | PMC |
| http://dx.doi.org/10.1016/j.virol.2019.10.016 | DOI Listing |
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