Proteomics

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Identification of components in protein complex of influenza A virus PA protein


ABSTRACT: Influenza A virus is mainly transmitted through the respiratory route and can cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to facilitate viral replication and 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 conducted immunoprecipitation and LC-MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, H3N2, and H7N9 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 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Cell Line Cell

DISEASE(S): Influenza

SUBMITTER: Chih-Ching Wu  

LAB HEAD: Chih-Ching Wu

PROVIDER: PXD050585 | Pride | 2024-06-23

REPOSITORIES: Pride

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Publications

Exploration of influenza A virus PA protein-associated cellular proteins discloses its impact on mitochondrial function.

Wu Chih-Ching CC   Tam Ee-Hong EH   Shih Yu-Yin YY   Lin Yi-Ru YR   Hsueh Pei-Chun PC   Shen Hsiang-Yi HY   Woung Chian-Huey CH   Wang Li-Ting LT   Tsai Jia-Chen JC   Lin Syh-Jae SJ   Chang Chuang-Rung CR   Ke Po-Yuan PY   Kuo Rei-Lin RL  

Virus research 20240513


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 proc  ...[more]

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