2. Academic Validation
  3. SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus

SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus

  • Adv Sci (Weinh). 2022 Oct 18;e2203088. doi: 10.1002/advs.202203088.
Qiuchen Li 1,  Zhimin Jiang 1 2,  Shuning Ren 1,  Hui Guo 2,  Zhimin Song 2,  Saini Chen 1,  Xintao Gao 3,  Fanfeng Meng 1,  Junda Zhu 1,  Litao Liu 1,  Qi Tong 1,  Honglei Sun 1,  Yipeng Sun 1,  Juan Pu 1,  Kin-Chow Chang 4,  Jinhua Liu 1
Affiliations

Affiliations

  • 1 Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
  • 2 Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 3 Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
  • 4 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, LE12 5RD, UK.
PMID: 36257906 DOI: 10.1002/advs.202203088
Abstract

Splicing of influenza A virus (IAV) RNA is an essential process in the viral life cycle that involves the co-opting of host factors. Here, it is demonstrated that induction of host serine and arginine-rich splicing factor 5 (SRSF5) by IAV facilitated viral replication by enhancing viral M mRNA splicing. Mechanistically, SRSF5 with its RRM2 domain directly bounds M mRNA at conserved sites (M mRNA position 163, 709, and 712), and interacts with U1 small nuclear ribonucleoprotein (snRNP) to promote M mRNA splicing and M2 production. Mutations introduced to the three binding sites, without changing amino acid code, significantly attenuates virus replication and pathogenesis in vivo. Likewise, SRSF5 conditional knockout in the lung protects mice against lethal IAV challenge. Furthermore, anidulafungin, an approved Antifungal drug, is identified as an inhibitor of SRSF5 that effectively blocks IAV replication in vitro and in vivo. In conclusion, SRSF5 as an activator of M mRNA splicing promotes IAV replication and is a host-derived Antiviral target.

Keywords

SRSF5; U1 snRNP; alternative splicing; anidulafungin; influenza A viruses.

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