Nakayama Emi E, Shingai Yasuhiro, Kono Ken, Shioda Tatsuo
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita-Shi, Osaka, Japan.
Virology. 2008 Jun 5;375(2):514-20. doi: 10.1016/j.virol.2008.02.028. Epub 2008 Mar 25.
Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that binds to the capsid protein of human immunodeficiency virus type 1 (HIV-1). TRIM5alpha is an antiretroviral factor influencing species-specific retroviral replication in Old World monkey (OWM) cells. In the study reported here, we investigated the role of CypA in anti-HIV-1 activity of OWM cells. Exogenous expression of CypA inhibited HIV-1 infection in OWM cells but not in human cells when the function of TRIM5alpha was suppressed by overexpression of dominant negative form of TRIM5alpha as well as by using RNA interference. This inhibitory action depended upon the interaction of the CypA moiety with HIV-1 capsid and disruption of CypA and capsid interaction by cyclosporine A enhanced the HIV-1 susceptibility of OWM cells even in the absence of functional TRIM5alpha. These results point to the presence of novel TRIM5alpha-independent anti-HIV-1 activity mediated by CypA in OWM cells.
亲环素A（CypA）是一种肽基脯氨酰异构酶，可与人免疫缺陷病毒1型（HIV-1）的衣壳蛋白结合。TRIM5α是一种抗逆转录病毒因子，影响旧世界猴（OWM）细胞中物种特异性逆转录病毒的复制。在本文报道的研究中，我们研究了CypA在OWM细胞抗HIV-1活性中的作用。当通过显性负性形式的TRIM5α过表达以及使用RNA干扰抑制TRIM5α的功能时，CypA的外源性表达抑制了OWM细胞中的HIV-1感染，但在人细胞中则没有。这种抑制作用取决于CypA部分与HIV-1衣壳的相互作用，并且即使在没有功能性TRIM5α的情况下，环孢素A破坏CypA与衣壳的相互作用也会增强OWM细胞对HIV-1的易感性。这些结果表明，在OWM细胞中存在由CypA介导的新型TRIM5α非依赖性抗HIV-1活性。
