Human Immunodeficiency Virus (HIV)-1 Integration Sites in Viral Latency

The persistence of human immunodeficiency virus type 1 (HIV-1) in latent reservoirs is a major barrier to HIV cure. Reservoir establishment depends on low viral expression that may be related to provirus integration sites (IS). In vitro, in cell lines and primary T cells, latency is associated with specific IS through reduced viral expression mediated by transcriptional interference by host cellular promoters, reverse orientation, and the presence of specific epigenetic modifiers. In primary T cell models of latency, specific IS are associated with intracellular viral antigen expression that is not directly related to cell activation. In contrast, in patient CD4+ T cells, there is enrichment for IS in genes controlling cell cycle and survival and in some clonally expanded T cell subpopulations. Multiple insertion sites within some specific genes may suggest that integrated HIV can increase the host’s T cell survival.