Recent Evolutionary History of HIV-1 Subtype B--Rebuttal

Abstract The history of the HIV-1 B epidemic is the subject of a continuing debate. Did the epidemic start in the 1970s, as it was established based on the epidemiological data, or decades earlier, as it was suggested based on the analysis of nucleotide distances in the env gene? Our study [Lukashov and Goudsmit,J Mol Evol (2002) 54: 680-691] found that the overestimation of the age of the epidemic in the analysis of env sequences was a bias resulting from the non-clock-like evolution at nonsynonymous sites, while the estimates based on synonymous substitutions agreed with the results of epidemiological studies. Besides the principal difference between the evolution of synonymous and nonsynonymous sites, several issues have to be addressed: (i) the onset of the HIV/AIDS epidemic, and not the circulation of the preepidemic viruses, should be taken as the gold standard for the timeline of HIV diversification; (ii) the circulation of ancient, preepidemic, viruses, whether long- or short-term, does not influence the increase of HIV divergence during the epidemic; and (iii) application of the same random latency probability for all viruses, irrespective to their age and distance from the common ancestor, biases the estimation of the age of the epidemic.[PUBLICATION ABSTRACT]