HIV-1 Nef蛋白最新功能及其增强病毒感染性分子机理的研究进展

Functions of HIV-1 Nef and How It Enhances Viral Infectivity

Nef蛋白是人类免疫缺陷病毒Ⅰ型（HIV-1）及其他灵长类动物慢病毒编码的一种附属蛋白,在获得性免疫缺陷综合症（AIDS）疾病进程和病毒的复制过程中起着重要作用。抑制附属蛋白活性的策略可以改善传统抗逆转录病毒方案的疗效,因此深入理解这一附属蛋白的功能和其分子作用机制具有重要意义。Nef蛋白通过三个主要活性调节宿主细胞环境,增强病毒复制。下调细胞表面分子如CD4,MHC-Ⅰ,MHC-Ⅱ等的表达,使病毒逃逸宿主的免疫应答;通过调节T细胞的信号通路降低T细胞的活化,从而营造有利于病毒复制的环境;直接增强新生子代病毒粒子的感染性。这一功能的分子机制直到最近宿主限制性因子丝氨酸转运蛋白（SERINC5）的发现才得以明晰。本文总结了Nef的功能及其增强病毒感染性的最新研究进展,同时也归纳了SERINC5蛋白与Nef蛋白的相互作用的研究报道,为深入了解病毒复制机理,改善HIV-1防治方案提供新的理论线索。

Nef is an auxiliary protein of lentiviruses.It is encoded by nef within the genomes of the primate lentiviruses human immunodeficiency virus（HIV）-1,HIV-2 and Simian immunodeficiency virus（SIV）.This protein is required for the maintenance of high viral load and disease progression,such as acquired immune deficiency syndrome（AIDS）.Updated knowledge of the mechanism（s）of Nef could lead to novel anti-retroviral strategies to prevent/delay HIV pathogenesis.Nef is a multifunctional protein that regulates the environment of host cells and enhances the replication of virions through various mechanisms：Nef downmodulates the surface levels of important molecules,such as cluster of differentiation-4,major histocompatibility complex（MHC）-Ⅰ and MHC-Ⅱ,to escape the host′s immune response;Nef can alter T-cell activation,and favor preliminary virus replication before massive stimulation following exposure to mitogens;Nef enhances the intrinsic infectivity of progeny virions through a mechanism involving the novel host restriction factor SERINC3/5.Here,we review the current knowledge surrounding Nef activities and discuss how Nef enhances the infectivity of HIV-1 virions.