Emerging recombinant human immunodeficiency viruses: uneven representationof the envelope V3 region

Objective: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombi nant genomes. Materials and methods: The envelope C2-C5 and the gag p24-p7 regions from o ne hundred infants infected perinatally in Tanzania were compared using phy logenetic and recombination analysis. Exact binomial and Fisher's exact tes ts were used to assess if various genomic regions were more likely to be ov errepresented in intersubtype recombinants. Results: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) s howed exclusively subtype A sequence in gag and env. Subtype C accounted fo r twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seve n 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 sequen ces were preferentially represented in the gag of A-D recombinants (P = 0.0 003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 r egion of subtype A was generally surrounded by subtype A C3-C5 sequences. I n 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 th e number of subtype A or subtype C sequences in A-C recombinants. Conclusion: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombina tion patterns showed that the V3 region of subtypes A or C was always selec ted in A-D and C-D recombinants. This selection suggests that the fitness o f 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 transm itted perinatally suggests that co-infection or super-infection by two HIV- 1 subtypes is not uncommon in this population. (C) 1999 Lippincott Williams & Wilkins.