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.

Virus Research
|May 8, 2024
PubMed

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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