Interactome Analysis of the NS1 Protein Encoded by Influenza A H1N1 Virus Reveals a Positive Regulatory Role of Host Protein PRP19 in Viral Replication

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• 作者：Rei-Lin Kuo ; Zong-Hua Li ; Li-Hsin Li ; Kuo-Ming Lee ; Ee-Hong Tam ; Helene M. Liu ; Hao-Ping Liu ; Shin-Ru Shih ; Chih-Ching Wu
• 刊名：Journal of Proteome Research
• 出版年：2016
• 出版时间：May 6, 2016
• 年：2016
• 卷：15
• 期：5
• 页码：1639-1648
• 全文大小：436K
• 年卷期：0
• ISSN：1535-3907

文摘

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.