Applications of CRISPR/Cas9 tools in deciphering the mechanisms of HIV-1 persistence

HIV-1 infection can be controlled but not cured by combination antiretroviral therapy. Indeed, the virus persists in treated individuals in viral reservoirs, the best described of which consisting in latently infected central memory CD4⁺ T cells. However, other cell types in other body compartments than in the peripheral blood contribute to HIV-1 persistence. Addressing the molecular mechanisms of HIV-1 persistence and their cell-specific and tissue-specific variations is thus crucial to develop HIV-1 curative strategies. CRISPR/Cas9 editing technologies have revolutionized genetic engineering by their high specificity and their versatility. Multiple applications now allow to investigate the molecular mechanisms of HIV-1 persistence. Here, we review recent advances in CRISPR-based technologies in deciphering HIV-1 gene expression regulation during persistence.