Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries

Abstract

The HIV-1 subtype A variant dominating the HIV-1 epidemics in former Soviet Union (FSU) countries (A(FSU)) represents one of the major clades of the HIV-1 pandemic. This variant was reported to have begun spreading among injecting drug users (IDUs) in the Ukrainian city of Odessa in late 1994. Two competing hypotheses have been proposed on the ancestral origin of the A(FSU) variant, locating it either in the Democratic Republic of Congo (DRC) or in the Republic of Guinea (RG). The studies supporting these hypotheses employed phylogenetic analyses to identify HIV-1 sequences collected outside FSU countries ancestrally related to A(FSU). A different approach, based on Bayesian phylogenetic inference and coalescent-based population genetics, has been employed here to elucidate the ancestry of this HIV-1 variant and to improve our knowledge on its spread in FSU countries. The analyses were carried out using env (C2-V3-C3) and p24(gag) fragments of the HIV-1 genome. The inferred migration for the HIV-1 A(FSU) variant revealed only one significantly supported migration pathway from Africa to Eastern Europe, supporting the hypothesis of its origin in the DRC and estimating the upper limit of the migration of the ancestral virus from Africa around 1970. The support for an origin in the RG was negligible. The results supported the main role of Odessa as the epicenter of the A(FSU) epidemic, dating the tMRCA of the A(FSU) variant around 1984, ten years before its explosive expansion among IDUs. The estimated origin of the AFSU subcluster responsible for the IDU outbreak was also located in Odessa, with the estimated tMRCA around 1993. Statistically supported migration routes from Odessa to other cities of Ukraine, Russia, Kazakhstan, Uzbekistan and Belarus were also inferred by the Bayesian phylogeographic analysis. These results shed new light on the origin and spread of the HIV-1 A(FSU) variant.