Requirement for cyclophilin A for the replication of vesicular stomatitis virus New Jersey serotype
Requirement for cyclophilin A for the replication of vesicular stomatitis virus New Jersey serotype
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DOI：
10.1099/vir.0.19074-0
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发表时间：
2003-07-01
影响因子：
3.8
通讯作者：
Banerjee, AK
中科院分区：
文献类型：
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作者：
Bose, S;Mathur, M;Banerjee, AK
一些宿主蛋白已被证明在水疱性口炎病毒（VSV）的生命周期中发挥关键作用。我们已经确定了另一种宿主蛋白，亲环蛋白A (CypA)，一种具有肽基顺式-反式脯氨酸异构酶活性的伴侣蛋白，是VSV复制所需的细胞因子之一。环孢素A （cyclosporin A, CsA）或SDZ-211-811抑制细胞CypA酶活性，导致VSV New Jersey （VSV- nj）血清型基因表达受到显著抑制，而这两种药物对VSV Indiana （VSV- ind）血清型基因组表达的影响显著降低。CypA催化失活突变体的过表达导致VSV-NJ复制减少，这表明VSV-NJ感染需要功能性CypA。在感染细胞中，CypA与VSV-NJ和VSV-IND的核衣壳蛋白相互作用，并被合并到两种血清型释放的病毒粒子中。VSV-NJ利用CypA进行进入后的细胞内初级转录，因为CsA抑制CypA可使VSV-NJ的初级转录降低85-90%，而VSV-IND的初级转录仅降低10%。因此，细胞CypA似乎与两种血清型VSV的N蛋白结合。然而，它对VSV-NJ的N蛋白活性起着强制性的作用，而对VSV-IND的N蛋白功能的要求则明显不那么重要。属于同一家族的两种血清学上不同的病毒对CypA的不同需求突出了它们在进化谱系中对特定宿主因子的利用。
Several host proteins have been shown to play key roles in the life-cycle of vesicular stomatitis virus (VSV). We have identified an additional host protein, cyclophilin A (CypA), a chaperone protein possessing peptidyl cis-trans prolyl-isomerase activity, as one of the cellular factors required for VSV replication. Inhibition of the enzymatic activity of cellular CypA by cyclosporin A (CsA) or SDZ-211-811 resulted in a drastic inhibition of gene expression by VSV New Jersey (VSV-NJ) serotype, while these drugs had a significantly reduced effect on the genome expression of VSV Indiana (VSV-IND) serotype. Overexpression of a catalytically inactive mutant of CypA resulted in the reduction of VSV-NJ replication, suggesting a requirement for functional CypA for VSV-NJ infection. It was also shown that CypA interacted with the nucleocapsid (N) protein of VSV-NJ and VSV-IND in infected cells and was incorporated into the released virions of both serotypes. VSV-NJ utilized CypA for post-entry intracellular primary transcription, since inhibition of CypA with CsA reduced primary transcription of VSV-NJ by 85-90%, whereas reduction for VSV-IND was only 10%. Thus, it seems that cellular CypA binds to the N protein of both serotypes of VSV. However, it performs an obligatory function on the N protein activity of VSV-NJ, while its requirement is significantly less critical for VSV-IND N protein function. The different requirements for CypA by two serologically different viruses belonging to the same family has highlighted the utilization of specific host factors during their evolutionary lineages.