Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses

Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within 2 months of childbirth. In addition, the env sequences from long-term-infected fetuses are highly divergent and form separate phylogenetic lineages from their cognate maternal viruses. Host-selection sites unique to neonate viruses are identified in regions frequently targeted by neutralizing antibodies and T cell immune responses. Identification of unique selection sites in the env gene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses. [Display omitted] Most in utero HIV-1 transmission occurs within 2 months of childbirthThe HIV-1 env gene sequences from long-term-infected fetuses are highly divergentSelection sites unique to fetal viruses are found in regions targeted by immunityPresence of selection sites indicates active adaptive immune responses in fetuses Marichannegowda et al. find that in utero transmission of HIV-1 usually occurs within 2 months of childbirth. Analysis of the env gene sequences from long-term-infected fetuses identifies host-selection signatures that are unique to viruses in infants, suggesting that the fetal immune system can exert selection pressure on viral evolution.