Kuo, Rei-LinRei-LinKuoHELENE MINYI LIULi, Zong-HuaZong-HuaLiLi, Li-HsinLi-HsinLiLee, Kuo-MingKuo-MingLeeTam, Ee-HongEe-HongTamLiu, Helene M.Helene M.LiuLiu, Hao-PingHao-PingLiuShih, Shin-RuShin-RuShihWu, Chih-ChingChih-ChingWu2018-09-102018-09-102016http://www.scopus.com/inward/record.url?eid=2-s2.0-84969142743&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/396441Influenza A virus, which can cause severe respiratory illnesses in infected individuals, is responsible for worldwide human pandemics. The NS1 protein encoded by this virus plays a crucial role in regulating the host antiviral response through various mechanisms. In addition, it has been reported that NS1 can modulate cellular pre-mRNA splicing events. To investigate the biological processes potentially affected by the NS1 protein in host cells, NS1-associated protein complexes in human cells were identified using coimmunoprecipitation combined with GeLC-MS/MS. By employing software to build biological process and protein-protein interaction networks, NS1-interacting cellular proteins were found to be related to RNA splicing/processing, cell cycle, and protein folding/targeting cellular processes. By monitoring spliced and unspliced RNAs of a reporter plasmid, we further validated that NS1 can interfere with cellular pre-mRNA splicing. One of the identified proteins, pre-mRNA-processing factor 19 (PRP19), was confirmed to interact with the NS1 protein in influenza A virus-infected cells. Importantly, depletion of PRP19 in host cells reduced replication of influenza A virus. In summary, the interactome of influenza A virus NS1 in host cells was comprehensively profiled, and our findings reveal a novel regulatory role for PRP19 in viral replication. ? 2016 American Chemical Society.influenza A virus; interactome; NS1; PRP19; RNA splicing/processing[SDGs]SDG3cell protein; nonstructural protein 1; small interfering RNA; transcriptome; DNA ligase; INS1 protein, influenza virus; nuclear protein; PRPF19 protein, human; RNA splicing factor; viral protein; Article; cell cycle; controlled study; embryo; host cell; human; human cell; immunoprecipitation; Influenza A virus (H1N1); nonhuman; priority journal; protein folding; protein protein interaction; RNA processing; RNA splicing; virus replication; chemistry; host pathogen interaction; Influenza A virus (H1N1); liquid chromatography; metabolism; physiology; procedures; proteomics; tandem mass spectrometry; Chromatography, Liquid; DNA Repair Enzymes; Host-Pathogen Interactions; Humans; Immunoprecipitation; Influenza A Virus, H1N1 Subtype; Nuclear Proteins; Proteomics; RNA Splicing Factors; Tandem Mass Spectrometry; Viral Nonstructural Proteins; Virus Replicationjournal article10.1021/acs.jproteome.6b00103