Two Highly Variable Vpr<sub>84</sub>and Vpr<sub>85</sub>Residues within the HIV-1-Vpr C-Terminal Protein Transduction Domain Control Transductionnal Activity and Define a Clade Specific Polymorphism

作     者：Jean-Herve Colle Thiery Rose Christine Rouzioux Alphonse Garcia 

作者机构：EA 3620 Universite Paris Descartes AP-HP Laboratoire de Virologie Hopital Necker Paris France Laboratoire E3 Phosphatases Unite Signalisation Moleculaire et Activation Cellulaire Institut Pasteur Paris France Unite d’Immunogenetique Cellulaire Institut Pasteur Paris France Unite de Biologie des Populations Lymphocytaires Institut Pasteur Paris France 

出 版 物：《World Journal of AIDS》 (艾滋病（英文）)

年 卷 期：2014年第4卷第2期

页      面：148-155页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：VPR HIV-1 Subtypes Polymorphism Transduction 

摘      要：The virally encoded HIV-1 viral protein R (VPR) is a multifunctional factor that is required for induced HIV-1 pathogenesis. VPR is also a cell-penetrating protein found in biological fluids from HIV-1 infected individuals. In this regard, we previously published that the C-terminal VPR77-92 sequence from HIV-1 89.6, but not from pNL4.3 strain, is a new pro-apoptotic and protein transduction domain (PTD). Here we report on a sequence analysis of VPR77-92 domain using the Los Alamos HIV-1 sequence database. The analysis showed that the two residues of the domain VPR84 and VPR85 are highly variable and differently biased in HIV-1 clade B and HIV-1 clade C. Furthermore, when Jurkat lymphoblastoid cells or PBMC were incubated with chemically synthesized peptides containing distinct VPR77-92 C-terminal sequences from clades B or C, we found that a clade-dependent polymorphism in VPR84 and VPR85 residues controlled the transducing activity of the C-terminal HIV-1 VPR77-92 domain. Together our data indicate that clade-dependent polymorphism in the VPR84 and VPR85?residues defines the transducing properties mediated by the C-terminal domain of HIV-1 VPR. Identification of this VPR polymorphism suggests new approaches to understand the HIV-1 biology and/or pathogenesis.