Deep-profiling identifies selection of non-synonymous amino acid substitutions in HIV-1 envelope during early infection.

Understanding the evolutionary dynamics of the viruses within an individual at or near the moment of transmission can provide critical inputs for the design of an effective vaccine for HIV infection. In this study, high throughput sequencing technology was employed to analyze the evolutionary rate in viruses obtained at a single time point from drug naïve recently infected infants and adults in the chronic stage of disease. Gene wise non-synonymous (pN) and synonymous (pS) mutation rates were estimated and compared between the two groups. Significant differences were observed in the evolutionary rates between viruses in the early and late stages of infection. Higher rates of adaptive mutations in env were found in the chronic viruses as compared to those in the early stages of HIV infection. Conversely, percentage of non-synonymous substitutions in env was found to be higher in recently transmitted viruses. In addition, a positive correlation was found between mutation and the evolutionary rate, and infectivity titer in recent infection. Despite the small sample size, the study identified useful information about viral evolution on transmission associated bottlenecks. The effect of intraindividual HIV-1 evolution at the population level was highly contemporary, and the higher percentage of non-synonymous substitutions seen in env during recent HIV-1 infection has suggested a pattern of convergent evolution leading to a positive selection for survival fitness and disease progression.