The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

Abstract

Background: Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time.

Materials and methods: Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples.

Results: Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005.

Conclusion: HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

Figure 1

Phylogenetic analysis of 51 HIV-1 pol (a) and 37 env (b) samples from Bolivia. Bootstrap values ≥70% supporting nodes are shown on the left of each node and were estimated using the neighbor-joining with Tamura-Nei substitution model. The scale bar indicates 10% nucleotide sequence divergence. HIV-1 samples analyzed in the present study were in bold format. Arrows indicate those samples with intergenic recombination. Highly supported (> 95%) monophyletic clusters are highlighted and numbered.

Figure 2

SplitsTree analysis of the HIV-1 Bolivian BF1 pol regions. The splits graph was constructed using NeighborNet methodology with pairwise distance input, which was estimated by F84 distance. The scale bar indicates 10% nucleotide sequence divergence. Reference sequences were indicated by subtype letter or CRF number. The alignment was prepared with HIV-1 group M subtypes B and F1 and CRF_BFs from South America. Four clusters containing studied samples were detected and are indicated with a circle. Representative bootscanning plots were generated for each cluster. Bootscan analysis was performed on a sliding window of 200 nt of the query sequences moving along an alignment of reference sequences by increments of 20 nt. Reference samples used for these analyses are discriminated in the figure legend.

Figure 3

Schematic representation of the BF1 mosaic structure from clusters 10, 11 and CRF12. Both genomic structures were drawn by using the Recombinant Draw Toll available in the Los Alamos homepage (http://www.hiv.lanl.gov/content/hiv-db/DRAW_CRF/recom_mapper.html).