Department of Dermatology, University of Erlangen/Nürnberg, D-91052 Erlangen, Germany.
Trends Microbiol. 2011 Sep;19(9):435-40. doi: 10.1016/j.tim.2011.06.002. Epub 2011 Jul 25.
After two decades of research the Nef protein of human immunodeficiency virus (HIV) remains a mysterious protein with an indisputable role in HIV pathogenesis. The ability to downregulate CD4 and major histocompatibility complex class I (MHC-I) was the first ascribed function of Nef and, whereas the number of downmodulated receptors by Nef is rising, so are the explanations for how their downregulation could contribute to HIV pathogenesis. At the same time there is increasing evidence that Nef not only induces endocytosis but also exocytosis, namely of cytokines and microvesicles that contain Nef itself. Because endocytosis and exocytosis are connected events, this is not surprising - and raises the intriguing possibility that HIV aims at secretion rather than ingestion. Have we therefore barked up the wrong tree over the past two decades? In this opinion article I argue that Nef-induced secretion is most probably the pathogenesis-relevant function behind this elusive viral effector.
经过二十年的研究，人类免疫缺陷病毒 (HIV) 的 Nef 蛋白仍然是一种神秘的蛋白质，它在 HIV 发病机制中具有不可争议的作用。下调 CD4 和主要组织相容性复合体 I (MHC-I) 的能力是最初归因于 Nef 的功能，而 Nef 下调的受体数量正在增加，因此对于其下调如何有助于 HIV 发病机制的解释也在增加。与此同时，越来越多的证据表明，Nef 不仅诱导内吞作用，还诱导胞吐作用，即包含 Nef 自身的细胞因子和微泡的胞吐作用。由于内吞作用和胞吐作用是相关联的事件，这并不奇怪——这提出了一个有趣的可能性，即 HIV 的目的是分泌而不是摄取。因此，在过去的二十年里，我们是否走错了方向？在这篇观点文章中，我认为，Nef 诱导的分泌很可能是这种难以捉摸的病毒效应物背后与发病机制相关的功能。
