Accurate predictions of population-level changes in sequence and structural properties of HIV-1 Env using a volatility-controlled diffusion model

作者：Orlando DeLeon, Hagit Hodis, Yunxia O’Malley, Jacklyn Johnson, Hamid Salimi, Yinjie Zhai, Elizabeth M. Winter, Claire Remec, Noah Eichelberger, Brandon Van Cleave, Ramya Puliadi, Robert Harrington, Jack T. Stapleton, Hillel Haim · 发表于：PLoS Biology · 年份：2017 · DOI：10.1371/journal.pbio.2001549 · 被引用次数：29 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Hepatitis C virus research

The envelope glycoproteins (Envs) of HIV-1 continuously evolve in the host by random mutations and recombination events. The resulting diversity of Env variants circulating in the population and their continuing diversification process limit the efficacy of AIDS vaccines. We examined the historic changes in Env sequence and structural features (measured by integrity of epitopes on the Env trimer) in a geographically defined population in the United States. As expected, many Env features were relatively conserved during the 1980s. From this state, some features diversified whereas others remained conserved across the years. We sought to identify "clues" to predict the observed historic diversification patterns. Comparison of viruses that cocirculate in patients at any given time revealed that each feature of Env (sequence or structural) exists at a defined level of variance. The in-host variance of each feature is highly conserved among individuals but can vary between different HIV-1 clades. We designate this property "volatility" and apply it to model evolution of features as a linear diffusion process that progresses with increasing genetic distance. Volatilities of different features are highly correlated with their divergence in longitudinally monitored patients. Volatilities of features also correlate highly with their population-level diversification. Using volatility indices measured from a small number of patient samples, we accurately predict the population diversity...