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The epidemic origin and molecular properties of B′: a founder strain of the HIV-1 transmission in Asia

Objective:To clarify the epidemic origin and molecular properties of the B′ subtype that is an important strain in the HIV-1 epidemic in Asia. Design:The genealogical relationship between the B′ and B subtype was investigated with two globally representative datasets covering the gag and env regions. B′ sequences were identified, from which the epidemic origin, population genetics and the signature mutation sites of the B′ subtype were inferred. Methods:Two globally representative datasets were compiled, using phylogenetic methods. Through coalescent-based analysis, the genealogical relationship between the B′ and B subtypes was investigated. The divergence times and population genetic parameters of B′ were estimated in a Bayesian framework using Markov Chains Monte Carlo sampling under a relaxed molecular clock method. Additionally, molecular properties of the B′ were identified by performing comparative sequence analysis with the HIV-1 M group. Results:About 15 years later after the B subtype began to spread, the B′ diverged from the B subtype. The demographic history of B′ was reconstructed, and the epidemic of B′ was estimated to originate around 1985. Eight and nine distinct signature mutation sites, unique to B′, were found around the p17 and V3 regions, respectively. Conclusion:Our research is the first large-scale investigation on HIV-1 B′ at a global level and provides a deep insight into one of the founder strains of HIV-1 epidemic in Asia. Our results provide an important reference for HIV scientists, public health officials and HIV vaccine designers.