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SRSF5 介导的 M 基因可变剪接对于流感 A 病毒复制至关重要：针对流感病毒的宿主定向靶标。

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

机构信息

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.

Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Adv Sci (Weinh). 2022 Dec;9(34):e2203088. doi: 10.1002/advs.202203088. Epub 2022 Oct 18.

DOI:10.1002/advs.202203088
PMID:36257906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9731694/
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.

摘要

流感病毒（IAV）RNA 的剪接是病毒生命周期中的一个重要过程，涉及到宿主因子的共调控。在这里，研究表明，IAV 诱导宿主丝氨酸/精氨酸丰富剪接因子 5（SRSF5）的表达，通过增强病毒 M mRNA 的剪接促进病毒复制。在机制上，具有 RRM2 结构域的 SRSF5 可直接在保守位点（M mRNA 位置 163、709 和 712）结合 M mRNA，并与 U1 小核核糖核蛋白（snRNP）相互作用，促进 M mRNA 的剪接和 M2 的产生。引入三个结合位点而不改变氨基酸编码的突变，可显著降低病毒在体内的复制和发病能力。同样，肺组织中 SRSF5 的条件敲除可保护小鼠免受致死性 IAV 攻击。此外，已批准用于抗真菌的安尼拉芬被鉴定为 SRSF5 的抑制剂，可有效抑制体外和体内的 IAV 复制。总之，作为 M mRNA 剪接的激活剂，SRSF5 促进了 IAV 的复制，是一种宿主来源的抗病毒靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/81a58db7ab20/ADVS-9-2203088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/cfa258b1d131/ADVS-9-2203088-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/1146bb1c856e/ADVS-9-2203088-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/c7bb14d1b1e6/ADVS-9-2203088-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/587e8d7077bf/ADVS-9-2203088-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/2b497885a800/ADVS-9-2203088-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/0b49e479ae28/ADVS-9-2203088-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/81a58db7ab20/ADVS-9-2203088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/cfa258b1d131/ADVS-9-2203088-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/1146bb1c856e/ADVS-9-2203088-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/c7bb14d1b1e6/ADVS-9-2203088-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/587e8d7077bf/ADVS-9-2203088-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/2b497885a800/ADVS-9-2203088-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/0b49e479ae28/ADVS-9-2203088-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3965/9731694/81a58db7ab20/ADVS-9-2203088-g001.jpg

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2
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EMBO J. 2022 Jan 4;41(1):e107640. doi: 10.15252/embj.2021107640. Epub 2021 Nov 15.
3
Synergistic in-vitro antiviral effects of combination treatment using anidulafungin and T-1105 against Zika virus infection.
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Int J Mol Sci. 2025 Apr 10;26(8):3584. doi: 10.3390/ijms26083584.
4
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Mol Cell Proteomics. 2024 Nov;23(11):100856. doi: 10.1016/j.mcpro.2024.100856. Epub 2024 Oct 9.
5
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6
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7
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