Unravelling the complicated evolutionary and dissemination history of HIV-1M subtype A lineages.

Subtype A is one of the rare HIV-1 group M (HIV-1M) lineages that is both widely distributed throughout the world and persists at high frequencies in the Congo Basin (CB), the site where HIV-1M likely originated. This, together with its high degree of diversity suggests that subtype A is amongst the fittest HIV-1M lineages. Here we use a comprehensive set of published near full-length subtype A sequences and A-derived genome fragments from both circulating and unique recombinant forms (CRFs/URFs) to obtain some insights into how frequently these lineages have independently seeded HIV-1M sub-epidemics in different parts of the world. We do this by inferring when and where the major subtype A lineages and subtype A-derived CRFs originated. Following its origin in the CB during the 1940s, we track the diversification and recombination history of subtype A sequences before and during its dissemination throughout much of the world between the 1950s and 1970s. Collectively, the timings and numbers of detectable subtype A recombination and dissemination events, the present broad global distribution of the sub-epidemics that were seeded by these events, and the high prevalence of subtype A sequences within the regions where these sub-epidemics occurred, suggest that ancestral subtype A viruses (and particularly sub-subtype A1 ancestral viruses) may have been genetically predisposed to become major components of the present epidemic.