11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:2 (abstract no. Mo.02)
McCutchan FE, Salminen MO, Carr JK, Burke DS; Henry M. Jackson Foundation, Rockville, MD, USA. Fax: 301-762-7460. E-mail: fmccutchan@hiv.hjf.org.

INTRODUCTION: HIV-1 evolves by the rapid accumulation of mutations and by recombination; both processes are actively contributing to its genetic diversity. Many new full-length sequences of HIV-1 isolates have been obtained, permitting, for the first time, a complete evaluation both of the genetic relationships among subtypes and of the breakpoints in inter-subtype recombinants. A revised classification of HIV group M subtypes and the common features of recombinant forms will be presented.

METHODS: DNA from primary virus cultures on donor PBMC was used as template for long PCR amplification of virtually full-length HIV-1 genomes. PCR products were molecularly cloned, sequenced, and analyzed by bootscanning and other methods. Subtype inter-relationships and recombination breakpoints were determined.

RESULTS: Full length genomic sequences of HIV-1 subtypes A, B, C, D, E, and G have been evaluated, together with several A/D recombinant forms. Subtypes A through D are largely, if not entirely distinguishable in gag, pol, env, vif, vpr, vpu, tat, rev, nef, and in the LTRs. In contrast, all available sequences of subtypes E and G are recombinant. Full length sequences of subtypes F, H, I, and J are unavailable, leaving open the possibility that some of these are also recombinants. In the recombinant forms, multiple breakpoints occur; some appear to be recurrent in independently derived recombinants. All available subtype E and G and some A/D recombinant HIV have retained the cytoplasmic domain of gp41 from clade A, suggesting selection for this segment. Some of the recombinants possess the matrix and core of one clade and the outer envelope of another, resembling virus pseudotypes. Recombinant HIV have already established a global reservoir and are responsible for the rapidly expanding epidemic in Southeast Asia. Increasing geographic intermixing of HIV subtypes may foster an expanded role for recombinant HIV in the future.

CONCLUSION: Exchanges of genetic material between HIV subtypes may represent a common adaptive strategy with significant functional and epidemiological implications.

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