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

Renjifo, Borisa; Gilbert, Peterb; Chaplin, Betha; Vannberg, Fredrika; Mwakagile, Davisc; Msamanga, Gernardd; Hunter, Davide; Fawzi, Wafaief; Essex, Maxa

Basic Science: Original Papers

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 recombinant genomes.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

From the aHarvard AIDS Institute, the bDepartment of Biostatistics, the eDepartment of Epidemiology and the fDepartment of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA, the cDepartment of Microbiology and Immunology and the dDepartment of Community Health, Muhimbili Medical Centre, Dar es Salaam, Tanzania.

Correspondence to Max Essex, Harvard AIDS Institute, 651 Huntington Avenue, Boston, MA 02115-6017, USA. Tel: +1 617 432 2334; fax: +1 617 739 8348; e-mail: messex@sph.harvard.edu

Received: 9 February 1999; revised: 12 May 1999; accepted: 9 June 1999.

© 1999 Lippincott Williams & Wilkins, Inc.