Vpr and HIV-1 disease progression : R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients

Vpr (viral protein R) is a 96 amino acid sol. protein that is expressed late during viral replication. Recent studies have focused on the role of a mutation at position 77 that might be assocd. with the condition of long-term non-progression, but data are still controversial. Fifteen long-term non-progressors (LTNP), 19 therapy-naive HIV-1-infected patients with progressive disease (Pr), 23 HIV-1-infected patients receiving sub-optimal therapy with dual nucleoside [nucleoside reverse transcriptase inhibitor (NRTI)] therapy but efficiently controlling viral replication (STP) and 19 antiretroviral therapy multi-experienced patients with actively replicating virus (MEP) were analyzed. HIV-RNA was extd. from plasma samples, the Vpr region was amplified, cloned and sequenced. The Pol gene was amplified, directly sequenced and analyzed using Sequence Navigator software. A significantly higher prevalence of the R77Q mutation was evidenced both in LTNP (86.7%) and STP (73.9%) in comparison with Pr (42.1%) and MEP (42.1%), (P= 0.007). Comparing groups of patients with progressive disease (Pr + MEP) and groups with non-progressive disease (LTNP + STP) the probability of harboring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P= 0.001). Our results support the hypothesis of the assocn. of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. R77Q does not seem to be linked to a particular viral strain but might be assocd. with immunol. selection. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr. [on SciFinder (R)]