Recombination in AIDS viruses

David L. Robertson, Beatrice H. Hahn, Paul M. Sharp

Recombination contributes to the generation of genetic diversity in human immunodeficiency viruses (HIV) but can only occur between viruses replicating within the same cell. Since individuals have not been found to be simultaneously coinfected with multiple divergent strains of HIV-1 or HIV-2, recombination events have been thought to be restricted to the rather closely related members of the quasispecies that evolves during the course of HIV infection. Here we describe examples of both HIV-1 and HIV-2 genomes that appear to be hybrids of genetically quite divergent viruses. Phylogenetic analyses were used to examine the evolutionary relationships among multiple HIV strains. Evolutionary trees derived from different genomic regions were consistent with respect to most of the viruses investigated. However, some strains of HIV-1 and HIV-2 exhibited significantly discordant branching orders indicative of genetic exchanges during their evolutionary histories. The crossover points of these putative recombination events were mapped by examining the distribution of phylogenetically informative sites supporting alternative tree topologies. A similar example of a recombinant simian immunodeficiency virus identified in West African green monkeys has also been described recently. These results indicate that coinfection with highly divergent viral strains can occur in HIV-infected humans and SIV-infected primates and could lead to the generation of hybrid genomes with significantly altered biological properties. Thus, future characterization of primate lentiviruses should include careful phylogenetic investigation of possible genomic mosaicism.