Roeth Jeremiah F, Collins Kathleen L
Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Microbiol Mol Biol Rev. 2006 Jun;70(2):548-63. doi: 10.1128/MMBR.00042-05.
The Nef protein of primate lentiviruses is a unique protein that has evolved in several ways to manipulate the biology of an infected cell to support viral replication, immune evasion, pathogenesis, and viral spread. Nef is a small (25- to 34-kDa), myristoylated protein that binds to a collection of cellular factors and acts as an adaptor to generate novel protein interactions to accomplish specific functions. Of the many biological activities attributed to Nef, the reduction of surface levels of the viral receptor (CD4) and antigen-presenting molecules (major histocompatibility complex class I) has been intensely examined; recent evidence demonstrates that Nef utilizes multiple, distinct pathways to affect these proteins. To accomplish this, Nef promotes the formation of multiprotein complexes, recruiting host adaptor proteins to commandeer intracellular vesicular trafficking routes. The altered trafficking of several other host molecules has also been reported, and an emerging theory suggests that Nef generates pleiotrophic effects in the secretory and endocytic pathways that reprogram intracellular protein trafficking and may ultimately provide an efficient platform for viral assembly. This review critically discusses some of the major findings regarding the impact of human immunodeficiency virus type 1 Nef on host protein transport and addresses some emerging directions in this area of human immunodeficiency virus biology.
灵长类慢病毒的Nef蛋白是一种独特的蛋白质，它通过多种方式进化，以操控被感染细胞的生物学特性，从而支持病毒复制、免疫逃逸、发病机制和病毒传播。Nef是一种小分子量（25至34千道尔顿）的肉豆蔻酰化蛋白，它能与一系列细胞因子结合，并作为衔接蛋白产生新的蛋白质相互作用以完成特定功能。在众多归因于Nef的生物学活性中，病毒受体（CD4）和抗原呈递分子（主要组织相容性复合体I类）表面水平的降低已得到深入研究；最近的证据表明，Nef利用多种不同途径来影响这些蛋白质。为实现这一点，Nef促进多蛋白复合物的形成，招募宿主衔接蛋白来掌控细胞内囊泡运输途径。也有报道称其他几种宿主分子的运输发生了改变，一种新出现的理论认为，Nef在分泌和内吞途径中产生多效性作用，重新编程细胞内蛋白质运输，最终可能为病毒组装提供一个高效平台。本综述批判性地讨论了一些关于人类免疫缺陷病毒1型Nef对宿主蛋白运输影响的主要发现，并探讨了人类免疫缺陷病毒生物学这一领域的一些新出现的研究方向。
