View All Abstracts for Session 48
261 Molecular Characterization of CTL Epitopes among Prevalent Brazilian HIV-1 Subtypes
M. Guimarães, A. Moreira, and M. Morgado*
IOC, Oswaldo Cruz Fndn., Rio de Janeiro, Brazil
Background: Several immunologically relevant epitopes for humoral and cellular immune responses have been described along the HIV-1 genome. The aim of this study was to evaluate the genetic polymorphism of selected regions for vaccine design among prevalent Brazilian HIV-1 subtypes and recombinant viruses.
Methods: Thirty-four HIV-1 samples previously subtyped by env-HMA were selected for this study: 7 of subtype B, 7 of C, 8 of F, 2 of D, 1 of A, and 9 corresponding to the B Brazilian subtype B variant. These samples were amplified in the env (C2-V3 and gp41), gag (p17), and nef regions for DNA sequencing by automatic method (ABI model 377). After sequence edition (GCG), phylogenetic and molecular evolutionary analyses were conducted using MEGA version 2.0 and ClustalW packages.
Results: Phylogenetic analysis based on the DNA sequencing of the 3 studied regions confirmed the presence of 9 (26.5%) potentially HIV-1 recombinant genomes. From the 8 gp120 subtype F samples analyzed, only 2 seemed to be “pure” F. Three other potentially HIV-1 recombinant viruses presented Bgag/Cenv (2) and Cgag/ Benv (1) patterns, respectively. Three molecular motifs could be identified on the top of V3 region: GPGR in B and F subtypes; GPGQ in subtypes C, D, and A; and GWGR, in B subtype B variant. Other intersubtype conserved amino acid substitutions were also observed in this region. The 5 portion of the gp120 C3 region was highly variable among all samples independent of the subtype. Typical molecular signatures could be observed for subtypes B, C, F, and D, both in a major gp41 CTL epitope (ERLKDQLL), as well as in the ELDKWAS gp41 neutralizing epitope. Although only few non-subtype B samples have already been analyzed so far, the CTL epitopes encoded in the nef region seemed to be relatively conserved among the subtypes with few amino acid substitutions. Only 3 out of 8 subtype F env samples were also F in the gag region however, an intra-subtype F typical signature was observed for the SLYNTVATL conserved gp17 CTL epitope, which was also highly polymorphic among the subtype B samples.
Conclusions: The variability of the HIV-1 subtypes on the immunologically relevant epitopes should be taken into account for vaccine design.
Contact Author about this Abstract
