Cyclophilin A protects mice against infection by influenza A virus.
Cyclophilin A protects mice against infection by influenza A virus.
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亲环蛋白 A 保护小鼠免受甲型流感病毒感染
DOI：
10.1038/srep28978
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发表时间：
2016-06-29
影响因子：
4.6
通讯作者：
Liu W
中科院分区：
文献类型：
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作者：
Li J;Chen C;Wong G;Dong W;Zheng W;Li Y;Sun L;Zhang L;Gao GF;Bi Y;Liu W
我们前期的研究表明亲环素A（Cyclophilin A，CypA）在体外能抑制甲型流感病毒的复制。为进一步研究CypA的抗病毒作用并探讨其作用机制，本研究建立了以SPC（CypA-SPC）或CMV（CypA-CMV）为双特异性启动子的CypA转基因小鼠。在用A/WSN/33（H1N1）流感病毒攻击后，与野生型动物相比，CypA-SPC和CypA-CMV转基因小鼠对病毒感染的抗病性分别增强了近2.5倍和3.8倍。病毒复制，病理损伤和炎症细胞因子在两个系的转基因小鼠中大大减少。此外，感染后，有一个上调的基因与细胞迁移，免疫功能和器官发育;和下调的基因与免疫细胞和细胞凋亡的阳性调节CypA过表达转基因小鼠（CypA+）的腹腔巨噬细胞。这些结果表明CypA是小鼠流感病毒抗性的关键调节剂，并且CypA+小鼠构成了研究CypA在免疫应答和感染调节中的作用的重要模型。
Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virusin vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections.