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EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death
Caitlin W Lehman1,2, Amy Smith1,2, Jamie Kelly3
1Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Viruses
|June 24, 2022
Summary
Early growth response 1 (EGR1) drives inflammatory gene expression and cell death in virus-infected astrocytoma cells. Targeting inflammation, like PTGS2, can protect cells from viral-induced death, crucial for managing neuroinflammation.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Early growth response 1 (EGR1) is upregulated in Venezuelan equine encephalitis virus (VEEV)-infected human astrocytoma cells.
- EGR1 loss reduces cell death but doesn't affect VEEV replication.
- The role of EGR1 in viral infection-induced gene expression requires further investigation.
Purpose of the Study:
- To determine the impact of EGR1 on gene expression following viral infection.
- To investigate EGR1's role in infections caused by various alphaviruses and other related viruses.
- To explore therapeutic strategies targeting EGR1-mediated inflammation.
Main Methods:
- Analysis of gene expression in virus-infected astrocytoma cells, focusing on EGR1 and downstream targets.
- Infection of astrocytoma cells with VEEV, eastern equine encephalitis virus (EEEV), Sindbis virus (SINV), chikungunya virus (CHIKV), Zika virus (ZIKV), and Rift Valley fever virus (RVFV).
- Inhibition of the inflammatory gene PTGS2 using Celecoxib to assess its effect on cell death and viral titers.
Main Results:
- EGR1 partially controlled the upregulation of inflammatory genes (CXCL3, CXCL8, CXCL10, TNF, PTGS2) and transcription factors (ATF3, FOS, JUN, KLF4, EGR2, EGR4) in VEEV-infected cells.
- EGR1 was upregulated in astrocytoma cells infected with EEEV, CHIKV, RVFV, SINV, and ZIKV, with varying degrees of dependency for downstream gene expression.
- Celecoxib treatment inhibited PTGS2, rescuing cells from VEEV-induced death without affecting viral load.
Conclusions:
- EGR1 induction upon viral infection stimulates multiple inflammatory mediators, contributing to cell death.
- Targeting EGR1-mediated inflammatory pathways, such as PTGS2, offers a potential therapeutic strategy against viral-induced neuropathology.
- Understanding EGR1's role is critical for managing neuroinflammation and cell death, particularly in VEEV infections with neurological sequelae.
