An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells

作者：Huang, Xiaofeng; Zheng, Min; Wang, Pui; Mok, Bobo Wing-Yee; Liu, Siwen; Lau, Siu-Ying; Chen, Pin; Liu, Yen-Chin; Liu, Honglian; Chen, Yixin; Song, Wenjun; Yuen, Kwok-Yung; Chen, Honglin^*

来源：Nature Communications, 2017, 8(1): 14751.

DOI：10.1038/ncomms14751

• VIRAL MESSENGER-RNA
• H7N9 VIRUS
• NUCLEOCYTOPLASMIC TRANSPORT
• BINDING PROTEINS
• HUMAN INFECTIONS
• NUCLEAR EXPORT
• GENOME
• CHINA
• EVOLUTION
• GENESIS

Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2-ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells.

• 出版日期2017-3-21
• 单位香港中文大学; 暨南大学; 厦门大学; 香港大学