HIV-1的病毒感染性因子（Vif）被揭示。

The viral infectivity factor (Vif) of HIV-1 unveiled.

作者信息

Rose Kristine M, Marin Mariana, Kozak Susan L, Kabat David

机构信息

Department of Biochemistry and Molecular Biology, Oregon Health and Science University Portland, Oregon 97239-3098, USA.

出版信息

Trends Mol Med. 2004 Jun;10(6):291-7. doi: 10.1016/j.molmed.2004.04.008.

DOI:10.1016/j.molmed.2004.04.008

PMID:15177194

Abstract

The viral infectivity factor (Vif) of HIV type-1 (HIV-1) is essential for efficient viral replication, yet was, until recently, enigmatic. This resulted from the complexity and cellular specificity of its function and the correspondingly complex systems that are required for its investigation. These limitations have been overcome and Vif function has been rapidly elucidated, with implications for the development of drugs to block its activity. These studies have revealed a novel component of the innate immune system, APOBEC3G, that lethally hypermutates retroviruses, including HIV-1. For HIV-1, the competition between the virus and APOBEC3G is tipped in favor of the invader by Vif, which binds to APOBEC3G and triggers its polyubiquitination and rapid degradation, thereby preventing its entry into progeny virions.

摘要

1型人类免疫缺陷病毒（HIV-1）的病毒感染因子（Vif）对于病毒的高效复制至关重要，但直到最近，其作用机制仍不清楚。这是由于其功能的复杂性和细胞特异性，以及研究所需的相应复杂系统所致。这些限制现已被克服，Vif的功能已迅速得到阐明，这对开发阻断其活性的药物具有重要意义。这些研究揭示了天然免疫系统的一个新成分——载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G），它能使包括HIV-1在内的逆转录病毒发生致命的高度突变。对于HIV-1而言，Vif使病毒与APOBEC3G之间的竞争向入侵者倾斜，Vif与APOBEC3G结合并引发其多聚泛素化和快速降解，从而阻止其进入子代病毒颗粒。