Cyclophilin A inhibits rotavirus replication by facilitating host IFN-I production
Cyclophilin A inhibits rotavirus replication by facilitating host IFN-I production
复制标题
亲环蛋白 A 通过促进宿主 IFN-I 的产生来抑制轮状病毒复制
DOI：
10.1016/j.bbrc.2012.05.050
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发表时间：
2012-06-15
影响因子：
3.1
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
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作者：
He, Haiyang;Zhou, Daijun;Wu, Yuzhang
轮状病毒（RV）感染会导致婴儿和新生动物严重的脱水性腹泻。我们以前的研究表明，亲环素A（CYPA），肽基脯氨酰顺反异构酶（PPlase），可以暂时上调RV感染的MA 104细胞在感染的早期阶段（未发表的数据）。为了研究CYPA在RV感染中的作用，我们通过基因转染和shRNA技术在不同的细胞系中过表达和沉默CYPA。我们发现CYPA的转染显著抑制RV复制，而沉默CYPA的表达显著增加RV复制。因此，CYPA的过表达显著增加了IFN-β的产生;而沉默CYPA显著降低了IFN-β的产生。CYPA对IFN-β产生的这种作用与其PPase活性无关。而且。在RV感染中宿主细胞分泌的IFN-β对病毒复制具有关键的抑制作用。最后，我们发现，通过SP 600125和JNK siRNA抑制JNK通路，消除了CYPA对RV感染的MA 104细胞中IFN-β转录的影响。总之，我们的数据表明，CYPA通过促进宿主IFN-β的产生来抑制RV复制，这与CYPA的PPase活性无关，但依赖于JNK信号通路的激活。(C)2012 Elsevier Inc. All rights reserved.
Rotavirus (RV) infection causes serious dehydrating diarrhoea in infants and newborn animals. Our previous study revealed that cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase (PPlase), could be temporarily upregulated in RV-infected MA104 cells in early stage of infection (unpublished data). To find out the possible roles of CYPA in RV infection, we overexpressed and silenced CYPA in various cell lines by gene transfection and shRNA. We found that transfection of CYPA significantly inhibited RV replication, while silencing the expression of CYPA significantly increased RV replication. Accordingly, overexpression of CYPA significantly increased IFN-beta production; while silencing CYPA significantly reduced IFN-beta production. This effect of CYPA on IFN-beta production was independent of its PPlase activity. Moreover. IFN-beta secreted by host cells in RV infection had a critical repressive effect on viral replication. Finally, we found that inhibiting JNK pathway by SP600125 and JNK siRNA abrogated the effect of CYPA on IFN-beta transcription in RV-infected MA104 cells. Together, our data suggested that CYPA inhibited RV replication by facilitating host IFN-beta production, which was independent on the PPlase activity of CYPA but dependent on the activation of JNK signaling pathway. (C) 2012 Elsevier Inc. All rights reserved.