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Published on: June 3, 2012
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.
Abstract:
Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack host cellular machinery for its replication. Host cells have evolved diverse cellular defense to resist the invasion of viruses. As the main components of promyelocytic leukemia protein nuclear bodies (PML-NBs), PML can inhibit the replication of many medically important viruses including IAV. However, the mechanism of PML against IAV is unclear. In the present study, we found PML was induced in response to IAV infection and ectopic expression of PML could inhibit IAV replication, whereas knockdown of endogenous PML expression could enhance IAV replication. Further studies showed that PML increased the expression of FBXW7 by inhibiting its K48-linked ubiquitination and enhanced the interaction between FBXW7 and SHP2, which negatively regulated IAV replication during infection. Moreover, PML stabilized RIG-I to promote the production of type I IFN. Collectively, these data indicated that PML inhibited IAV replication by enhancing FBXW7 expression in the antiviral immunity against influenza virus and extended the mechanism of PML in antiviral immunity.
Insights
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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