Caracterização da variabilidade antigênica do genedo envelope (env) em amostras de HIV-1 circulantesno Distrito Federal
The HIV-1 is characterized by a high genetic diversity. Such diversity haspotential implication on the local epidemiology of AIDS. This work aimed to describethe inter-subtype and intra-subtype variability of HIV-1 isolates circulating in theFederal District, Central Brazil. Fifty-three RNA samples, of the year 2002, from aPublic Health Laboratory of Federal District were reversely transcribed.Complementary DNA were amplified by nested PCR to obtain a fragment of 564 bp,corresponding to the env C2/C3 region. The PCR products were automaticallysequenced. The sequences obtained were analyzed by the REGA. Subtypes identifiedwere B 53 (96.2%), F 1 (1.9%) and B/F 1 (1.9%). Phylogenetic analysis based on theC2/C3 env DNA sequence from the HIV-1 isolates analyzed was 100% concordant withREGA results. These data were complemented with the subtype characterization basedon gag, pol and nef, to evaluate the genetic diversity of HIV-1 isolates in thisgeographic region. We observed discordance in 8 samples (15%), all presented mosaicgenomic B/F forms. The amino acid sequences of 41 HIV-1 isolates were analyzed forthe genetic and antigenic intra-subtype diversity. High heterogeneity was observed atthe tetrapeptide on tip of the V3 loop in the subtype B variants. The most prevalent wasthe GPGR (50%) typical in the U.S./European strains, followed by the Brazilian variantB??(GWGR), (10%), the GFGR (7.5%) and GPGK (7.5%) motifs and the GLGR motif(5%). Other V3 variants were found in 8 isolates (20%): GPGN, GPGA, GPGY,GQGR, GPGS, ALGR, APGG, GPGH. The tetrapeptide sequences GPGY and ALGRwere not previously described in the literature. Amino acids with positively charge atthe position 11 and/or 25, at the V3 loop, were also analyzed. It was observed that 22%of the HIV-1 isolates presented charged residues at these positions, suggesting a X4 andsyncytium-inducing profile. As the V3 loop is considered to be important forneutralizing antibodies and corecpetor recognition, the presence of such variability inthis genomic region may have considerable implications on vaccine design and immuneresponse. This study may contribute to the understanding of HIV-1 geneticpolymorphism in Brazil, and may prove useful for the development of appropriate anti-HIV vaccines in the Federal District.
Advisor:Andrea Queiroz Maranhao; Silviene Fabiana de Oliveira; Cláudia Renata Fernandes Martins
School:Universidade de Brasília
Source Type:Master's Thesis
Date of Publication:03/20/2006