Transcriptional profiling of CD4+T cells derived from HIV-1 elite controllers

Stansell, Alexander Colin
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HIV-1 is still a substantial cause of morbidity and mortality worldwide. It infects CD4+T cell subsets, where it establishes a latent reservoir of virus that cannot be cleared by host immune responses. In most individuals, progressive infection leads to immune collapse and the development of opportunistic pathogens and cancers that cause mortality. Within all HIV-1 patients a small subset known as elite controllers establish stringent immune control over HIV-1 without the need for antiretroviral therapy. Transcriptional differences in CD4+T cell subsets with in the context of elite control have yet to be fully described. This study used RNA sequencing data to transcriptionally profile Naive (TN), Central Memory (TCM) and Effector Memory (TEM) CD4+T cell subsets derived from HIV-1 elite controllers. It aimed to identify differences in immune control mechanisms between T cell subsets. This project used stringent quality processing, normalisation, alignment and quantification methods to ascertain gene expression level, and identify transcriptional differences in T cell subsets and co-expressed gene networks. Three distinct methodologies for identifying co-expressed genes were compared. Findings showed similarities between TCM and TEM subsets, that likely reflect commonalities in their differentiation states, as well as between TN and TCM subsets that likely reflect commonalities in function. TN and TEM subsets were found to have the greatest number of differences with respect to their transcriptional profiles; which upon further investigation, were found to reflect differences in viral transcription, differentiation and cellular activation
Dissertation Submitted to the Faculty of Science, University of the Witwatersrand n fulfilment of the requirements for the degree of Master of Science, 2020