P24.19
Background: The advent of next generation sequencing technology has provided a sensitive platform for producing extensive datasets that allow novel and detailed analyses of viral adaption and immune control of HIV. In the context of expression of HLA alleles associated with superior viral control and slow disease progression, in particular HLA-B*27:05 and HLA-B*57:01, intrahost population diversity revealed through the minor variant data produced may provide critical insights into the determinants of immune control.
Methods: We performed full-length HIV high-throughput Illumina sequencing on a cohort of subjects expressing both HLA-B*27:05 and HLA-B*57:01, including two transmission pairs and eleven additional individuals, with longitudinal sampling of six subjects. The HLA-B*27:05/B*57:01 positive group included both HIV controllers and progressors.
Results: In order to evaluate the determinants of HLA-mediated control of HIV, we have conducted an analysis of the minor variant populations and their impact on immune control, comparing intrahost variability across the full genome and at CD8+ T Cell epitopes in HLA-B*27:05/B*57:01 positive controllers versus non-controllers. We describe changes in intrahost variability over time, and analyse the evolution of the donor founder virus in the context of HLA-B*27:05/B*57:01 expression in the transmission pairs. In an HLA-B*27:05/B*57:01 positive progressor we show that accumulation of escape mutations at low levels in the minor variants precedes fixation of these mutations within the population and predicts disease progression.
Conclusions: The novel insights afforded through use of next generation sequencing technology may be critical for furthering our understanding of intrahost viral evolution and immune control. Particularly in the context of expression of favourable HLA alleles, these insights may provide important information for informing HIV T cell vaccine design.
