Quaranta Maria Giovanna, Mattioli Benedetta, Giordani Luciana, Viora Marina
Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
FASEB J. 2006 Nov;20(13):2198-208. doi: 10.1096/fj.06-6260rev.
Dendritic cells (DC) play a crucial role in the generation and regulation of immunity, and their interaction with HIV is relevant in the pathogenesis of AIDS favoring both the initial establishment and spread of the infection and the development of antiviral immunity. HIV-1 Nef is an essential factor for efficient viral replication and pathogenesis, and several studies have been addressed to assess the possible influence of endogenous or exogenous Nef on DC biology. Our findings and other reported data described in this review demonstrate that Nef subverts DC biology interfering with phenotypical, morphological, and functional DC developmental programs, thus representing a viral tool underlying AIDS pathogenesis. This review provides an overview on the mechanism by which Nef, hijacking DC functional activity, may favor both the replication of HIV-1 and the escape from immune surveillance. Overall, the findings described here may contribute to the understanding of Nef function, mechanism of action, and cellular partners. Further elucidation of genes induced through Nef signaling in DC could reveal pathways used by DC to drive HIV spread and will be critical to identify therapeutic strategies to bias the DC system toward activation of antiviral immunity instead of facilitating virus dissemination.
树突状细胞（DC）在免疫的产生和调节中发挥着关键作用，它们与HIV的相互作用在艾滋病发病机制中具有重要意义，既有利于感染的初始建立和传播，也有利于抗病毒免疫的发展。HIV-1 Nef是病毒高效复制和发病机制的一个重要因素，已有多项研究致力于评估内源性或外源性Nef对DC生物学的可能影响。我们的研究结果以及本综述中描述的其他已报道数据表明，Nef通过干扰DC的表型、形态和功能发育程序来颠覆DC生物学，因此它是艾滋病发病机制的一种病毒工具。本综述概述了Nef劫持DC功能活性从而可能有利于HIV-1复制和逃避免疫监视的机制。总体而言，此处描述的研究结果可能有助于理解Nef的功能、作用机制和细胞伙伴。进一步阐明DC中通过Nef信号诱导的基因，可能会揭示DC驱动HIV传播所使用的途径，对于确定使DC系统偏向于激活抗病毒免疫而非促进病毒传播的治疗策略至关重要。
