Immune-Based Strategies for HIV Cure Research

Biomarker discovery in latently infected single cells

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Suppressive antiretroviral therapy has been successful in control HIV-associated disease. However, the need for long-term patient care makes elimination of the latent HIV reservoir from the body a highly desirable goal. Studying the latent reservoir has been hampered by the low frequency of latently infected cells, the presence of these cells in diverse human tissues that are difficult to sample, and our fundamental lack of understanding of the cell types in which latent HIV can reside. In this study, we proposal to use a combination of powerful technologies - namely, single cell isolation, latent cell identification by DNAscope and RNAscope, and whole transcriptome analysis by RNAseq - to gain an understanding of the transcriptional programming of latently infected cells. A key focus of the work will be analyzing transcriptomes of single cells, providing detailed information about the population heterogeneity of single latently infected cells, the differences in their gene expression programs as compared to uninfected and actively infected cells, and candidate biomarkers that provide strong discrimination potential between these cellular populations. Ultimately, the work will lay the foundation for future development of biomarkers and biomarker-based diagnostics and therapeutics.