Harvard Catalyst Profiles

HIV-1 reservoir cells harbor chromosomally-integrated viral DNA, persist lifelong and fuel rebound viremia upon treatment interruptions, thus representing the major barrier to a cure of HIV-1 infection. Although once considered completely resistant to host immune effects due to viral latency, these cells show, on closer inspection by high-resolution analytic techniques, discrete signs of selection by host immune responses, implying that at least some of these cells may be susceptible to immune recognition and immune-mediated elimination. Yet, very little is currently known about the influence of sex on immune activity against the viral reservoir cell pool, even though more than half of all people living with HIV-1 today are female, and female sex is associated with improved immune activity against HIV-1 during untreated infection, arguably best exemplified by an up to 4-fold higher probability of developing an elite controller phenotype. We have ongoing studies that focus on a detailed, high-resolution analysis of the molecular, phenotypic and transcriptional profile of HIV-1 reservoir cells in females and males on long-term ART. At this stage, the student is expected to use a pipeline of recently-developed assays in our lab to characterize proviral intactness, chromosomal integration sites and associated activating and inhibitory epigenetic chromatin modifications. The main hypothesis for this part of the study is that preferential accumulation of intact proviruses in repressive chromatin regions occurs more frequently and rapidly in females and leads to an integration site landscape dominated by genome-intact proviruses integrated in heterochromatin locations.