Sequence analysis of an HIV-1 subtype C acutely infected cohort from Durban, South Africa.
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The Human Immunodeficiency Virus is a global public health concern. The Joint United Nations Programme on HIV/AIDS estimated that 36.9 million people were infected with HIV globally at the end of 2017. Almost 20% of these resided in South Africa, making this the highest global HIV burden held by any one country. It is thus important that HIV infection be detected early as this may have important implications in the control of the pandemic. The early recognition of acute HIV infection could present early treatment options that could alter the natural history of the disease, or even eliminate infection. Detecting acute infection early could also provide a unique opportunity to understand HIV transmission and pathogenesis, including early host-virus interactions. In the present study, blood samples were collected from 18-23 year old HIV-1 subtype C acutely infected women from Umlazi Township in KwaZulu-Natal, South Africa, that had participated in a study called Females Rising through Education, Support and Health (FRESH). Eleven blood samples from this cohort, collected within 24 hours of onset of plasma viremia, were used for this study. The aim of the present research was to identify sites within pol that were experiencing positive selective pressure and the likely implications of these mutations on viral functional domains and host cytotoxic T-lymphocyte (CTL) epitopes. The study also sort to observe the loss of drug resistant mutations (DRM) in the viral sequences of participants who had multiple timepoints and to correlate mutation loss to structural changes. Datamonkey and Phylogenetic Analysis by Maximum Likelihood (PAML) were used to detect positively selected sites. Putative functional domains were detected using Prosite and CTL epitopes were identified using the Los Alamos Molecular Immunology Database. Ancestral reconstruction was performed using PAML and Bayesian Evolutionary Analysis by Sampling Trees (BEAST) was used to calculate the time to the most recent common ancestor. Altogether 16 unique positively selected sites were identified in this cohort. Putative functional domains were highly conserved in protease, while positive mutations in reverse transcriptase resulted in either a loss of functional domains in conserved regions or in the gain of functional sites in non-conserved regions. Owing to the important role that protease plays in viral maturation and infectivity, mutations within these conserved regions could possibly lead to defective viral particles with reduced viral infectivity. The K103N in reverse transcriptase, observed in one participant, was the only DRM inherited from its common ancestor. The major limitation of this study was the small sample size.