The Center for AIDS Health Disparities Research, Meharry Medical College , Nashville, Tennessee, USA.
Department of Microbiology, Immunology, and Physiology, Meharry Medical College , Nashville, Tennessee, USA.
J Virol. 2023 Nov 30;97(11):e0073223. doi: 10.1128/jvi.00732-23. Epub 2023 Oct 16.
The HIV-1 genome encodes a small number of proteins with structural, enzymatic, regulatory, and accessory functions. These viral proteins interact with a number of host factors to promote the early and late stages of HIV-1 infection. During the early stages of infection, interactions between the viral proteins and host factors enable HIV-1 to enter the target cell, traverse the cytosol, dock at the nuclear pore, gain access to the nucleus, and integrate into the host genome. Similarly, the viral proteins recruit another set of host factors during the late stages of infection to orchestrate HIV-1 transcription, translation, assembly, and release of progeny virions. Among the host factors implicated in HIV-1 infection, Cyclophilin A (CypA) was identified as the first host factor to be packaged within HIV-1 particles. It is now well established that CypA promotes HIV-1 infection by directly binding to the viral capsid. Mechanistic models to pinpoint CypA's role have spanned from an effect in the producer cell to the early steps of infection in the target cell. In this review, we will describe our understanding of the role(s) of CypA in HIV-1 infection, highlight the current knowledge gaps, and discuss the potential role of this host factor in the post-nuclear entry steps of HIV-1 infection.
HIV-1 基因组编码少量具有结构、酶、调节和辅助功能的蛋白质。这些病毒蛋白与许多宿主因子相互作用，促进 HIV-1 感染的早期和晚期阶段。在感染的早期阶段，病毒蛋白与宿主因子的相互作用使 HIV-1 能够进入靶细胞，穿越细胞质，在核孔处停靠，进入细胞核，并整合到宿主基因组中。同样，在感染的晚期阶段，病毒蛋白招募另一组宿主因子来协调 HIV-1 的转录、翻译、组装和产生新的病毒粒子。在参与 HIV-1 感染的宿主因子中，亲环素 A（CypA）被鉴定为第一个被包装在 HIV-1 颗粒中的宿主因子。现在已经明确，CypA 通过直接与病毒衣壳结合来促进 HIV-1 感染。确定 CypA 作用的机制模型从产生细胞中的作用扩展到靶细胞中感染的早期阶段。在这篇综述中，我们将描述我们对 CypA 在 HIV-1 感染中的作用的理解，强调当前的知识空白，并讨论这个宿主因子在 HIV-1 感染的核后进入步骤中的潜在作用。
