Bose Santanu, Mathur Manjula, Bates Patricia, Joshi Nikita, Banerjee Amiya K
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
J Gen Virol. 2003 Jul;84(Pt 7):1687-1699. doi: 10.1099/vir.0.19074-0.
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.
几种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。我们鉴定出一种额外的宿主蛋白，亲环素A（CypA），一种具有肽基顺反脯氨酰异构酶活性的伴侣蛋白，是VSV复制所需的细胞因子之一。环孢菌素A（CsA）或SDZ - 211 - 811对细胞CypA酶活性的抑制导致VSV新泽西州（VSV - NJ）血清型的基因表达受到显著抑制，而这些药物对VSV印第安纳州（VSV - IND）血清型的基因组表达影响明显较小。CypA催化无活性突变体的过表达导致VSV - NJ复制减少，表明VSV - NJ感染需要功能性的CypA。还显示CypA在感染细胞中与VSV - NJ和VSV - IND的核衣壳（N）蛋白相互作用，并被整合到两种血清型释放的病毒粒子中。VSV - NJ在进入细胞后的初级转录过程中利用CypA，因为用CsA抑制CypA可使VSV - NJ的初级转录减少85 - 90%，而VSV - IND仅减少10%。因此，细胞CypA似乎与两种VSV血清型的N蛋白结合。然而，它对VSV - NJ的N蛋白活性发挥必需功能，而对VSV - IND的N蛋白功能来说其需求的关键程度明显较低。同一科中两种血清学不同的病毒对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。
