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PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection
Mengwei Xu1, Huan Xu2, Weiwei Wan1
1State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
Viruses
|December 23, 2023
Summary
Researchers identified protein disulfide isomerase A4 (PDIA4) as crucial for lymphocytic choriomeningitis virus (LCMV) infection. Targeting PDIA4 offers a potential new strategy for developing antiviral therapies against LCMV.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Mammalian arenaviruses are zoonotic viruses causing severe hemorrhagic diseases.
- Lymphocytic choriomeningitis virus (LCMV) is a significant arenavirus with no available FDA-approved treatments.
- Host factors supporting LCMV replication remain incompletely understood.
Purpose of the Study:
- To identify host factors essential for LCMV infection using quantitative proteomic analysis.
- To investigate the role of protein disulfide isomerase A4 (PDIA4) in LCMV pathogenesis.
- To explore potential therapeutic targets against LCMV.
Main Methods:
- Quantitative proteomic analysis to identify host factors.
- Biochemical assays to determine viral component interactions.
- Endoplasmic reticulum stress (ERS) pathway manipulation (ATF6 inhibition).
Main Results:
- PDIA4 was identified as a critical host factor for LCMV infection.
- LCMV glycoprotein was found to upregulate PDIA4 expression.
- Inhibiting ATF6-mediated ERS reduced LCMV-induced PDIA4 upregulation.
- PDIA4 influences LCMV RNA synthesis and viral release.
Conclusions:
- PDIA4 plays a significant role in the LCMV life cycle.
- PDIA4 is a potential novel therapeutic target for LCMV antiviral drug development.
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