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Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
Exploration of influenza A virus PA protein-associated cellular proteins discloses its impact on mitochondrial
Chih-Ching Wu1, Ee-Hong Tam2, Yu-Yin Shih3
1Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Abstract:
Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LC‒MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.
Insights
The influenza A virus PA protein disrupts host cell mitochondria and triggers autophagy. This study identifies PYCR2 as a mitochondrial protein with an antiviral role against influenza A virus.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Influenza A virus causes severe respiratory illness by interacting with host factors.
- The viral PA protein is a key virulence factor influencing pathogenicity.
Purpose of the Study:
- To identify host cellular factors interacting with influenza A virus PA proteins.
- To investigate the role of PA protein in host biological processes, particularly mitochondrial function and autophagy.
Main Methods:
- Immunoprecipitation and LC–MS/MS to identify PA-interacting proteins.
- Immunofluorescence and mitochondrial fractionation to determine PA localization.
- Assays to assess mitochondrial respiration, autophagy, and viral replication.
Main Results:
- PA proteins from H1N1, 2009 pandemic H1N1, and H3N2 viruses interact with mitochondrial, proteasomal, and nuclear proteins.
- PA protein localizes to mitochondria, reduces mitochondrial respiration, and interacts with PYCR2.
- PA protein triggers autophagy and disrupts mitochondrial homeostasis, while PYCR2 exhibits antiviral activity.
Conclusions:
- Influenza A virus PA protein significantly impacts host mitochondrial function and induces autophagy.
- PA protein's interaction with PYCR2 and its effects on mitochondria are crucial for viral pathogenicity.
- Understanding these interactions offers potential targets for antiviral strategies.
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