Cyclophilin A restricts influenza A virus replication through degradation of the M1 protein.

Cyclophilin A restricts influenza A virus replication through degradation of the M1 protein.
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亲环蛋白 A 通过降解 M1 蛋白来限制甲型流感病毒复制

DOI:
10.1371/journal.pone.0031063
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Liu W
Liu W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu X;Zhao Z;Xu C;Sun L;Chen J;Zhang L;Liu W

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亲环素A(CypA)是肽基脯氨酰异构酶亲环素家族的典型成员,并且参与多种病毒的复制。以往的研究表明,CypA与流感病毒M1蛋白相互作用,破坏病毒复制的早期阶段。为了进一步理解CypA损害流感病毒复制的分子机制,建立了内源CypA缺失的293 T细胞系。结果表明CypA抑制病毒复制的起始。此外,在没有CypA的情况下,流感病毒的感染性增加。进一步的研究表明,CypA对病毒基因组复制或转录的阶段没有影响,也不损害病毒mRNA的核输出。然而,CypA降低了病毒蛋白水平。其他研究表明,CypA通过泛素/蛋白酶体依赖性途径增强M1的降解。我们的研究结果表明,CypA通过加速M1蛋白的降解来限制流感病毒的复制。
Cyclophilin A (CypA) is a typical member of the cyclophilin family of peptidyl-prolyl isomerases and is involved in the replication of several viruses. Previous studies indicate that CypA interacts with influenza virus M1 protein and impairs the early stage of the viral replication. To further understand the molecular mechanism by which CypA impairs influenza virus replication, a 293T cell line depleted for endogenous CypA was established. The results indicated that CypA inhibited the initiation of virus replication. In addition, the infectivity of influenza virus increased in the absence of CypA. Further studies indicated that CypA had no effect on the stages of virus genome replication or transcription and also did not impair the nuclear export of the viral mRNA. However, CypA decreased the viral protein level. Additional studies indicated that CypA enhanced the degradation of M1 through the ubiquitin/proteasome-dependent pathway. Our results suggest that CypA restricts influenza virus replication through accelerating degradation of the M1 protein.
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