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PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression.
Hai-Yan Yan1,2, Hui-Qiang Wang1,2, Ming Zhong1,2
1CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Virologica Sinica
|May 28, 2021
Summary
Promyelocytic leukemia protein (PML) inhibits influenza A virus (IAV) replication by boosting antiviral immunity. PML enhances FBXW7 expression and RIG-I stabilization, crucial for combating IAV infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Influenza A viruses (IAV) cause significant annual epidemics with high morbidity and mortality.
- IAV replication relies on hijacking host cellular machinery, necessitating robust host defense mechanisms.
- Promyelocytic leukemia protein (PML), a key component of PML nuclear bodies, is known to inhibit viral replication, but its precise mechanism against IAV remains elusive.
Purpose of the Study:
- To elucidate the mechanism by which PML inhibits influenza A virus (IAV) replication.
- To investigate the role of PML in host antiviral immunity against IAV.
- To determine how PML influences key cellular pathways involved in antiviral defense.
Main Methods:
- Investigated PML induction upon IAV infection.
- Assessed the effect of PML overexpression and knockdown on IAV replication.
- Analyzed PML's impact on FBXW7 expression and ubiquitination.
- Examined the interaction between FBXW7 and SHP2.
- Studied PML's effect on RIG-I stabilization and type I Interferon (IFN) production.
Main Results:
- PML expression is induced by IAV infection.
- Ectopic PML expression inhibits IAV replication, while PML knockdown enhances it.
- PML increases FBXW7 expression by preventing its K48-linked ubiquitination.
- PML promotes the interaction between FBXW7 and SHP2, which inhibits IAV replication.
- PML stabilizes RIG-I, leading to increased type I IFN production.
Conclusions:
- PML acts as a crucial antiviral factor against influenza A virus.
- PML inhibits IAV replication by enhancing FBXW7 expression and promoting FBXW7-SHP2 interaction.
- PML strengthens antiviral immunity through RIG-I stabilization and type I IFN production, expanding our understanding of PML's role in host defense.
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