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.