Testing the hypothesis of a recombinant origin of human immunodeficiency virus type 1 subtype E

The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been sugg ested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1 A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93 TH065) and from the Central African Republic (90CF11697 and 90CF4071), incr easing the total number of HIV-1E complete genome sequences available to se ven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger mon ophyletic group. The apparent phylogenetic incongruence at different region s of the genome that was previously taken as evidence of recombination is s hown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as eviden ce for recombination, can be misleading, particularly when there are differ ences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate sup port for the hypothesis that subtype E variants are derived from a recombin ant lineage. In contrast, many other HIV strains claimed to have a recombin ant origin, including viruses for which only a single parental strain was e mployed for analysis, do indeed satisfy the statistical criteria we propose . Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriat e assignments that would obscure the true evolutionary properties of these viruses.