Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences

Abstract

AbstractIn 2018, an estimated 38 million people lived with HIV-1 infection resulting in 770,000 deaths. More than 50% of this infection and its associated deaths occurred in Sub-Saharan Africa. There is the need to develop an HIV-1 vaccine if the epidemic would be effectively controlled. Cytotoxic T Lymphocytes (CTL) epitopes within the Major Hydrophobic Region (MHR) have been shown to be highly immunogenic and immuno-dominant. These conserved epitopes have recently been the focus of vaccines studies. Despite the West African epicenter having one of the highest numbers of diverse circulating HIV-1 strains, very few longitudinal studies have checked the frequencies of CTL immune escape variants on epitopes within and without the MHR for HIV-1 strains circulating in the region.In this study we describe non-synonymous substitutions within and without the MHR of HIV-1 GAG genes isolated from 10 infected Nigerians at the early stages of HIV-1 infection. Furthermore, we analyzed these substitutions longitudinally in five infected individuals from the early stages of infection up until when antibodies become detectable. We identified 3 non synonymous substitutions within the MHR of HIV-1 GAG genes isolated from the early HIV infected individuals. Fourteen and nineteen mutations outside the MHR were observed before and after detection of antibodies respectively while 4 mutations were found within the MHR. These substitutions include previously mapped CTL epitope immune escape mutants. CTL immune pressure likely leave different footprints on HIV-1 GAG epitopes within and outside the MHR. This information is crucial for future vaccine designs for use in the West African region.