Ernest Tee

The plenary today provided revolutionary insights on single-cell multiomic technology to measure and characterize the HIV reservoir. In addition, the key virological and immunological mechanisms underpinning natural and post-treatment HIV controllers were also described.

Ya-Chi Ho provided an overview of single-cell multiomics to evaluate the cellular landscape of the HIV reservoir, particularly the ECCITEseq and DOGMAseq single-cell modalities. Through ECCITEseq, she discovered that HIV-1 infected cells upregulated cytotoxic T-cell response genes, were capable of clonal proliferation, formed larger and more stable clonal populations, and predominantly comprised of cytotoxic CD4+ T-cells. Furthermore, HIV-infected CD4+ T-cells highly express Serpin B9, which could protect them from self-inflicted granzyme B toxicity, and also shield them from granzyme B-mediated injury from cytotoxic CD8+ T-cells. Using DOGMAseq, Ya-Chi showed that eight genes were upregulated in both latent and transcriptionally active HIV-1 cells. This includes the IKZF3 gene, which promoted the differentiation, survival and proliferation of infected CD4+ T-cells. Based on the combined DNA, RNA and proteomic output from DOGMAseq, she highlighted four distinct differentiation trajectories of HIV-1 infected T-cells, namely interferon activation, cytotoxic, AP-1 migration and cellular death resistance phenotypes. Asier Sáez-Cirión subsequently provided an overview of the virological and immunological mechanisms that underpin elite and post-treatment HIV controllers. He highlighted the importance of the multi-pronged innate immunity response; the coordinated neutralizing antibody response; and the development of enhanced CD8+ T-cells to control HIV infection in these individuals.

Single-cell multiomic analysis of the HIV reservoir provides a high-resolution map of both latent and transcriptionally active HIV reservoir. This improves the understanding of the mechanisms underlying the persistence of the HIV reservoir, which is an important step forward in the quest for HIV cure. Elite and post-treatment HIV controllers are valuable real-life resources to aid our understanding of the immunological and virological mechanisms underpinning their HIV control. This insight is critical for the development of future therapeutic and cure strategies for HIV.