title: Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication.
abstract: Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Sheng
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Gu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shijuan
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.|Key Laboratory of Tumor Targeted Drug in Guangdong Province, Guangzhou Double Bioproducts Co., Ltd., Guangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|International College, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000072283:A549 Cells; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C085820:INS1 protein, influenza virus; C107953:RAC1 protein, human; D017361:Viral Nonstructural Proteins; D020830:rac1 GTP-Binding Protein