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HIV1-病毒蛋白 R(Vpr)突变:相关表型及与临床病理学的关系。

HIV1-viral protein R (Vpr) mutations: associated phenotypes and relevance for clinical pathologies.

机构信息

FMUC-Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

CNC-Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.

出版信息

Rev Med Virol. 2016 Sep;26(5):314-29. doi: 10.1002/rmv.1889. Epub 2016 Jun 6.

Abstract

Over the last 30 years, research into HIV has advanced the knowledge of virus genetics and the development of efficient therapeutic strategies. HIV-1 viral protein R (Vpr) is a specialized and multifunctional protein that plays important roles at multiple stages of the HIV-1 viral life cycle. This protein interacts with a number of cellular and viral proteins and with multiple activities including nuclear transport of the pre-integration complex (PIC) to the nucleus, transcriptional activation, cell cycle arrest at G2/M transition phase and induction of cell death via apoptosis. Specifically, Vpr has been shown to control many host cell functions through a variety of biological processes and by interaction with several cellular pathways. The different functions of Vpr may enhance viral replication and impair the immune system in HIV-1 infected patients. Importantly, functional defects induced by mutations in the Vpr protein correlate with slow disease progression of HIV-infected patients. Vpr is also associated with other concomitant pathologies developed by these patients, which may lead it to be considered as a potential novel therapeutic target. This review will focus on HIV-1 Vpr, mainly on the importance of its structural mutations on the progression of HIV infection, associated phenotypes and relevance for clinical pathologies. Copyright © 2016 John Wiley & Sons, Ltd.

摘要

在过去的 30 年中,对 HIV 的研究推进了病毒遗传学知识和高效治疗策略的发展。HIV-1 病毒蛋白 R(Vpr)是一种专门的多功能蛋白,在 HIV-1 病毒生命周期的多个阶段发挥重要作用。该蛋白与许多细胞和病毒蛋白相互作用,并具有多种活性,包括将整合前复合物(PIC)核转运至细胞核、转录激活、细胞周期停滞在 G2/M 转换期以及通过细胞凋亡诱导细胞死亡。具体而言,Vpr 通过多种生物学过程和与多个细胞途径的相互作用来控制许多宿主细胞功能。Vpr 的不同功能可能会增强 HIV-1 感染患者中的病毒复制并损害免疫系统。重要的是,Vpr 蛋白突变引起的功能缺陷与 HIV 感染患者的疾病缓慢进展相关。Vpr 还与这些患者发生的其他伴随病理有关,这可能使其被认为是一种有潜力的新型治疗靶点。本综述将重点介绍 HIV-1 Vpr,主要关注其结构突变对 HIV 感染进展、相关表型和临床病理学相关性的重要性。版权所有 © 2016 约翰威立父子有限公司。

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