Interactome Analysis of the NS1 Protein Encoded by Influenza A H1N1 Virus Reveals a Positive Regulatory Role of Host Protein PRP19 in Viral Replication.
Influenza 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.
Rei-Lin
RL
Kuo
Zong-Hua
ZH
Li
Li-Hsin
LH
Li
Kuo-Ming
KM
Lee
Ee-Hong
EH
Tam
Department of Clinical Laboratory Sciences and Medical Technology, College of Medicine, National Taiwan University , Taipei 10617, Taiwan.
Helene M
HM
Liu
Department of Veterinary Medicine, National Chung Hsing University , Taichung 40227, Taiwan.
Hao-Ping
HP
Liu
Shin-Ru
SR
Shih
Chih-Ching
CC
Wu
D002853:Chromatography, Liquid; D045643:DNA Repair Enzymes / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry* / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D000072260:RNA Splicing Factors / Q000502:physiology*; D053719:Tandem Mass Spectrometry; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000378:metabolism*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D017361:Viral Nonstructural Proteins; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human
NS1; PRP19; RNA splicing/processing; influenza A virus; interactome