AEGiS-11IAC: Continuous in vivo recombination between HIV-1 strains of genetic subtypes A and C.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Continuous in vivo recombination between HIV-1 strains of genetic subtypes A and C.

Int Conf AIDS 1996 Jul 7-12; 11:228 (abstract no. Tu.A.511)
Salminen MO, Robertson DL, Sharp PM, Hahn BH, Burke DS, McCutchan FE; H.M. Jackson Foundation, Rockville, MD, USA. Fax: 301-762-7460. E-mail: msalminen@hiv.hjf.org.

INTRODUCTION: Recombination between two genetic subtypes of HIV-1 can occur, and clades A through H are known to have participated in these genetic exchanges. Recombinant forms are thought to result from double infections and homologous RNA recombination between the infecting strains, but it has not yet been established conclusively that recombinants occur in vivo. We have studied HIV-1 genomes from epidemiologically linked patients in Zambia from whom serial samples were available. Multiple different, but related, A/C inter-genotypic recombinants were found in both primary and cultured PBMCs.

METHODS: Serial samples obtained more than one year apart from the index case and a single sample from her spouse were analyzed. Complete genomes and/or full-length gag and env genes were PCR amplified using DNA from virus cultures on peripheral blood mononuclear cells (PBMCs) or from primary patient PBMCs, and were molecularly cloned and sequenced. DNA sequences were analyzed for the distribution of recombination breakpoints by bootscanning, by distance scanning, and by analysis of phylogenetically informative sites.

RESULTS: Analysis of a full-length HIV-1 genome from the virus culture of PBMCs obtained in 1990 from a Zambian woman established that the provirus was recombinant between subtypes A and C in gag, in pol, and in env. Virtually identical sequences were recovered from primary and from cultured PBMCs. The gag and env genes of the virus from a 1989 sample, and from a sample taken at the same time from the woman's husband, were closely related to the 1990 sequences but had different breakpoints. Furthermore, the breakpoints were not completely shared between the contemporaneous samples of the husband and wife.

CONCLUSIONS: These results establish that HIV-1 inter-genotypic recombination occurs in vivo, and that multiple recombinant forms can arise over time an infected individual. The predominance of different recombinant forms in serial samples suggests ongoing selection.

Keywords: AEGIS, HIV-1, Genes, env, Recombination, Genetic, Genes, gag, Genes, vpu, Proviruses, Genome, Viral, HIV-1 Reverse Transcriptase, Genes, pol, Polymerase Chain Reaction, Variation (Genetics), Zambia, Human, Female, genetics, ICA11

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