EVOLUTION AND PROBABLE TRANSMISSION OF INTERSUBTYPE RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN A ZAMBIAN COUPLE

The extraordinary genetic diversity of human immunodeficiency virus ty pe 1 (HIV-1) results from the introduction of mutations by an error-pr one reverse transcriptase and from recombination of the two RNA genome s packaged in the virion during the synthesis of proviral DNA. The occ urrence of multiple, genetically distant HIV-1 subtypes and their geog raphic intermixing set up conditions for dramatic, rather than gradual , changes in genotype whenever genomes from different subtypes are cop ackaged in virions. Here we describe, for the first time, the sequenti al generation of multiple different, but related, intersubtype HIV-1 r ecombinants within an infected individual. Full-length gag and env gen es were recovered directly from peripheral blood mononuclear cells or from primary virus cultures, using serial blood samples from a Zambian woman and a sample from her spouse. DNA sequencing and phylogenetic a nalysis established that two different A/C recombinant forms of HIV-1 predominated at two time points in the woman. A related but distinct r ecombinant HIV-1 was recovered from her spouse. Intersubtype recombina tion apparently played a central role in the evolution of HIV-1 in thi s couple and may contribute substantially to the rapid emergence of HI V-1 variants whenever mixed-subtype HIV-1 infections occur.