Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins.

Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins.
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亲环素A通过稳定病毒蛋白促进B型流感病毒的复制。

DOI:
10.1016/j.isci.2023.108515
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发表时间:
2023-12-15
期刊:
影响因子:
5.8
通讯作者:
Sun, Lei
Sun, Lei
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Li, Huizi;Fan, Wenhui;Min, Jie;Bai, Xiaoyuan;Yang, Wenxian;Li, Heqiao;Zhao, Yuna;Lin, Runshan;Jia, Xiaojuan;Liu, Wenjun;Sun, Lei

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B型流感每年流行,并在人类中造成严重的疾病负担。然而,对B型流感病毒(IBV)的感染机制知之甚少。在这里,我们发现宿主因子亲环素A(CypA)通过靶向IBV非结构蛋白1(BNS 1)和核蛋白(BNP)促进IBV复制。CypA通过上调OTUD 4表达促进OTUD 4介导的K48连接的BNS 1去泛素化以稳定BNS 1。同时,CypA和E3连接酶MIB 1竞争性地与BNP相互作用以抑制其蛋白酶体降解。此外,环孢菌素A处理或CypA R55 A突变导致CypA在IBV复制中的功能受损。值得注意的是,BNP通过增强BNP和IBV聚合酶碱性蛋白1之间的相互作用,将CypA劫持到细胞核中以增强病毒核糖核蛋白复合物的活性。综上所述,本研究揭示了CypA在促进IBV复制中的关键作用,表明CypA是抗IBV药物的有希望的靶点。CypA促进流感B病毒复制CypA通过上调OTUD 4表达促进BNS 1去泛素化CypA和MIB 1与BNP竞争性相互作用以抑制其降解BNP将CypA劫持到细胞核中以增强vRNP复合物的活性医学;病毒学;生物科学
Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1 (BNS1) and nucleoprotein (BNP). CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression. Meanwhile, CypA and the E3 ligase MIB1 competitively interact with BNP to inhibit its proteasomal degradation. Moreover, cyclosporine A treatment or CypA R55A mutation results in an impaired function of CypA in IBV replication. Notably, BNP hijacks CypA into the nucleus to enhance the activity of viral ribonucleoprotein complexes by enhancing the interaction between BNP and IBV polymerase basic protein 1. Taken together, this study unveils the critical role of CypA in facilitating IBV replication, suggesting that CypA is a promising target for anti-IBV drug. CypA facilitates influenza B virus replication CypA promotes BNS1 deubiquitination by upregulating OTUD4 expression CypA and MIB1 competitively interact with BNP to inhibit its degradation BNP hijacks CypA into the nucleus to enhance the activity of vRNP complexes Medicine; Virology; Biological sciences
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