Two Highly Variable Vpr₈₄and Vpr₈₅ Residues within the HIV-1-Vpr C-Terminal Protein Transduction Domain Control Transductionnal Activity and Define a Clade Specific Polymorphism

Jean-Herve Colle, Thiery Rose, Christine Rouzioux, Alphonse Garcia

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.

DOI: 10.4236/wja.2014.42019                

Abstract

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 VPR_77-92 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 VPR_77-92 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 VPR_77-92 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 VPR_77-92 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.

Keywords

VPR, HIV-1 Subtypes, Polymorphism, Transduction

Conflicts of Interest

The authors declare no conflicts of interest.

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