Molecular Mechanisms of HIV-1 Latency from a Chromatin and Epigenetic Perspective

Abstract Purpose of Review The main obstacle to an HIV-1 cure is the reservoir of HIV-1 infected cells. While antiretroviral therapy (ART) eliminates the HIV-1 virus effectively, it does not target the reservoir. To eliminate infected cells, we need an improved understanding of the reservoir maintenance and reactivation mechanisms, including the influence of chromatin. Recent Findings The last years’ technological advances enable an in-depth study of the reservoir, uncovering subsets of infected cells, proviral integration sites, and single-cell nucleosome histone modifications. These revelations illustrate how the immune system and cell proliferation shape reservoirs under long-term ART. These forces create highly individual reservoirs that will require personalized treatment for their eradication. Summary A greater understanding of HIV-1 latency mechanisms, focusing on chromatin features, proviral reservoir dynamics, and inter-individual differences, can drive the development of more precise HIV-1 treatment strategies, ultimately achieving a globally available HIV-1 cure.