Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region

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Abstract
To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher‚s exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P=0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P=0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P=0.0003) as well as C-D recombinants (P=0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.