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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.
Abstract:
Mammalian arenaviruses are rodent-borne zoonotic viruses, some of which can cause fatal hemorrhagic diseases in humans. The first discovered arenavirus, lymphocytic choriomeningitis virus (LCMV), has a worldwide distribution and can be fatal for transplant recipients. However, no FDA-approved drugs or vaccines are currently available. In this study, using a quantitative proteomic analysis, we identified a variety of host factors that could be needed for LCMV infection, among which we found that protein disulfide isomerase A4 (PDIA4), a downstream factor of endoplasmic reticulum stress (ERS), is important for LCMV infection. Biochemical analysis revealed that LCMV glycoprotein was the main viral component accounting for PDIA4 upregulation. The inhibition of ATF6-mediated ERS could prevent the upregulation of PDIA4 that was stimulated by LCMV infection. We further found that PDIA4 can affect the LCMV viral RNA synthesis processes and release. In summary, we conclude that PDIA4 could be a new target for antiviral drugs against LCMV.
Insights
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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