AEGiS-11IAC: Molecular epidemiology of HIV-1 in Venezuela.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Molecular epidemiology of HIV-1 in Venezuela.

Int Conf AIDS 1996 Jul 7-12; 11:32 (abstract no. LB.C.6049)
Quinones-Mateu ME, Pacheco M, Acevedo N, Domingo E; Centro de Biologia Molecular "Severo Ochoa," Madrid, Spain. Fax: 34-1-397-4799. E-mail: mquinone@mvax.cbm.uam.es.

OBJECTIVE: To analyze two groups of HIV-1 isolates from Venezuela (1991 and 1994/95) by HMA subtyping and to characterize sequence evolution for three different genomic regions in recent years.

METHODS: Twenty-eight blood samples from HIV-1 positive Venezuelan patients were obtained in two periods: March-Oct. 91 and Aug. 94-May 95. The HIV-1 serostatus and clinical profile of each subject were established. Proviral DNA was obtained and three genomic regions were amplified and sequenced for each sample: LTR region, the first exon of tat gene, and the C2V3-coding region of env. PCR products of an internal fragment spanning the V1-V5-coding region of gp120 were genetically compared with 14 previously characterized HIV-1 strains (subtypes A-H) by a heteroduplex mobility assay. Phylogenetic trees for the three regions were constructed using the neighbour-joining method and the statistical robustness was tested by boostrap resampling (1000 datasets). Genetic distances and mutant frequencies were determined for each studied region.

RESULTS: The analysis of heteroduplexes of the env PCR products of the Venezuelan samples and the reference sequences showed unequivocal electrophoretic patterns, corresponding to subtype B. These qualitative results were confirmed by phylogenetic analysis based on nucleotide sequences. In each tree derived from LTR, tat or C2V3-coding region, Venezuelan isolates clustered with subtype B viruses. Sub-clustering of the Venezuelan isolates was not seen in any tree analyzed. Pairwise comparisons of nucleotide sequences showed an average intraclade divergence of 7% (2 to 11%), 8% (0 to 15%), and 10% (2 to 14%) for LTR, tat, and C2V3, respectively. No differences were observed among genetic distances of both groups. Average point mutant frequencies, relative to the consensus defined by the samples under study, were 4.0 x 10(-2), 4.7 x 10(-2), and 5.2 x 10(-2) substitutions per nucleotide for LTR, tat, and C2V3, respectively. The results indicate a high variability for the studied regions.

CONCLUSIONS: Circulating HIV-1 identified in Venezuela belong to subtype B. Genetic distances for the three regions of both time periods were very similar. Nucleotide diversity of C2V3-coding region was comparable to that described for HIV-1 isolates from countries where the epidemic had started many years earlier. It is the first study that includes a phylogenetic analysis using LTR and tat regions. Mutant frequencies were similar to LTR, tat, and C2V3 sequences confirming the high variability for all HIV-1 genomic regions.

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LBC6049