Change of positive selection pressure on HIV-1 envelope gene inferred by early and recent samples.

HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo- and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures.