Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients.
BACKGROUND
Vpr (viral protein R) is a 96 amino acids soluble protein that is expressed late during viral replication. Recent studies have focused on the role of a mutation at position 77 that might be associated with the condition of long-term non-progression, but data are still controversial.


METHODS
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 analysed. HIV-RNA was extracted from plasma samples, the Vpr region was amplified, cloned and sequenced. The Pol gene was amplified, directly sequenced and analysed using Sequence Navigator software.


RESULTS
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 harbouring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P = 0.001).


CONCLUSIONS
Our results support the hypothesis of the association 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 associated to immunologic 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.
Mologni
Daniela
D
Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Milan, Italy.
Citterio
Paola
P
Menzaghi
Barbara
B
Zanone Poma
Barbara
B
Riva
Chiara
C
Broggini
Valentina
V
Sinicco
Alessandro
A
Milazzo
Laura
L
Adorni
Fulvio
F
Rusconi
Stefano
S
Galli
Massimo
M
Riva
Agostino
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D005260:Female; D015751:Genes, pol / Q000235:genetics; D016334:Genes, vpr / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D011897:Random Allocation; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics
D012367:RNA, Viral