Variability of the conserved V3 loop tip motif in HIV-1 subtype B isolates collected from Brazilian and French patients

Abstract

The diversity of the V3 loop tip motif sequences of HIV-1 subtype B was analyzed in patients from Botucatu (Brazil) and Montpellier (France). Overall, 37 tetrameric tip motifs were identified, 28 and 17 of them being recognized in Brazilian and French patients, respectively. The GPGR (P) motif was predominant in French but not in Brazilian patients (53.5% vs 31.0%), whereas the GWGR (W) motif was frequent in Brazilian patients (23.0%) and absent in French patients. Three tip motif groups were considered: P, W, and non-P non-W groups. The distribution of HIV-1 isolates into the three groups was significantly different between isolates from Botucatu and from Montpellier (P < 0.001). A higher proportion of CXCR4-using HIV-1 (X4 variants) was observed in the non-P non-W group as compared with the P group (37.5% vs 19.1%), and no X4 variant was identified in the W group (P < 0.001). The higher proportion of X4 variants in the non-P non-W group was essentially observed among the patients from Montpellier, who have been infected with HIV-1 for a longer period of time than those from Botucatu. Among patients from Montpellier, CD4+ cell counts were lower in patients belonging to the non-P non-W group than in those belonging to the P group (24 cells/µL vs 197 cells/µL; P = 0.005). Taken together, the results suggest that variability of the V3 loop tip motif may be related to HIV-1 coreceptor usage and to disease progression. However, as analyzed by a bioinformatic method, the substitution of the V3 loop tip motif of the subtype B consensus sequence with the different tip motifs identified in the present study was not sufficient to induce a change in HIV-1 coreceptor usage.

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients

“…There is evidence in the literature concerning the association between HIV GWG variant and slower disease progression in HIV mono-infected patients. [17–20,44] In this work, nevertheless we did not establish the direct association between the GWG variant and AIDS presence, cytopathic ability, or HIV risk factors in the mono-infected group (Table 2). However, it may be only a consequence of characteristics of the patients included in this study, in which aids presence was predominant (Table 1).…”

“…In this study, the frequency of the GWG variant (Table 1) is in agreement with recent reports from Southeast Brazil. [20,43]…”

“…Previous studies have demonstrated the association between the GWG variant and progression of HIV infection in mono-infected patients. [16–20] Importantly, the patients with the GWG variant present slower HIV infection progression and better prognosis. However, so far there are no reports concerning the association of the GWG HIV variant and infection evolution in HIV patients coinfected with hepatitis C virus (HCV).…”

Characterization of Primary Isolates of HIV Type 1 CRF28_BF, CRF29_BF, and Unique BF Recombinants Circulating in São Paulo, Brazil

“…53 Crucially, these findings provide further biological evidence that this motif (GWGR) alone does not determine the coreceptor usage. 54 Moreover, CXCR4-tropic viruses were more common than CCR5-tropic viruses (7 and 3, respectively), regardless of the recombination profile and patient clinical status. Furthermore, despite our limited sample size but because both in vitro and in silico procedures converged on CXCR4 usage determination, it is worthwhile to try to determine in greater detail whether the Geno2pheno algorithm may indeed increase accuracy in coreceptor usage prediction.…”

Caracterização biológica e molecular de recombinantes naturais de HIV-1.

“…Crucially, these findings provide further biological evidence that this motif (GWGR) alone does not determine the coreceptor usage 54 . Moreover, CXCR4-tropic viruses were more common than CCR5-tropic (7 and 3, respectively), regardless of the recombination profile and patient clinical status.…”