Jacotot, E., Ravagnan, L., Loeffler, M., Ferri, K.F., Vieira, H.L., Zamzami, N., Costantini, P., Druillenec, S., Hoebeke, J., Briand, J.P., Irinopoulou, T., Daugas, E., Susin, S.A., Cointe, D., Xie, Z.H., Reed, J.C., Roques, B.P. and Kroemer, G. (2000) The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore. Journal of Experimental Medicine, 191, 33-46.

has been cited by the following article:

• TITLE: 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

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

  KEYWORDS: VPR, HIV-1 Subtypes, Polymorphism, Transduction

  JOURNAL NAME: World Journal of AIDS, Vol.4 No.2, June 13, 2014

  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 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 VPR85residues 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.