Interactome analysis of the NS1 protein encoded by influenza A H1N1 virus reveals a positive regulatory role of host protein PRP19 in viral replication
Journal
Journal of Proteome Research
Journal Volume
15
Journal Issue
5
Pages
1639-1648
Date Issued
2016
Author(s)
Kuo, Rei-Lin
Li, Zong-Hua
Li, Li-Hsin
Lee, Kuo-Ming
Tam, Ee-Hong
Liu, Helene M.
Liu, Hao-Ping
Shih, Shin-Ru
Wu, Chih-Ching
Abstract
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. ? 2016 American Chemical Society.
Subjects
influenza A virus; interactome; NS1; PRP19; RNA splicing/processing
SDGs
Other Subjects
cell 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 Replication
Type
journal article