Frauke Mücksch

Characteristics of the viral reservoir and ways to achieve its reduction were discussed. Specifically, studies focussed on strategies for selective killing of cells harbouring intact proviruses, TFH cells in the spleen and lymph node reservoir, the role of glycolysis during latency reversal and novel scRNAseq analysis of HIV transcribing cells.

Steven Yukl (UCSF, USA) presented a study identifying the Bcl-2 inhibitor Obatoclax which caused selective killing of cells containing intact, but not total or defective proviruses, thus making this compound a suitable candidate for therapies designed to reduce the intact HIV reservoir. Joy Folkvord (University of Arizona, USA) showed that the majority of vRNA+ cells in spleens and approximately 50% of vRNA+ cells in lymph nodes were located in extrafollicular regions. Phenotyping of vRNA+ cells showed that very few of these cells had a TFH phenotype, suggesting that TFH cells are a minor source of the spleen and LN reservoir. Yetunde Kayode (Upstate Medical University, USA) showed that glycolysis is necessary for HIV-1 latency reversal and that LRAs are differentially dependent on glycolysis. LRAs induce histone acetylation and lactylation in a glycolysis-dependent fashion. Together, highlighting the importance of physiologically relevant conditions when screening LRAs. Sushama Telwatte (The Doherty Institute, Australia) presented a novel scRNA seq technique which improves detection of HIV RNA+ cells by 31% and increases the number of HIV transcripts detected per cell. This is achieved by incorporating custom HIV primers capturing HIV RNA into the 10X-pipeline. HIV-transcribing cells were enriched in the effector memory population.

A novel scRNA seq technique is valuable for future reservoir characterization as it improves detection of HIV RNA+ cells and allows for detection of non-polyadenylated HIV transcripts. TFH cells are a minor source of the HIV reservoir in spleen and LN. Obatoclax is a promising candidate for therapies designed to reduce the intact HIV reservoir and should be evaluated in vivo. In addition, future studies testing combinations of obatoclax and other drugs ex vivo and in animal and human trials will be valuable. Given the dependence of LRAs on glycolysis, LRA studies should be performed in physiologically relevant experimental conditions.