HIV persistence in subsets of CD4+T cells: 50 shades of reservoirs

Antiretroviral therapy controls HIV replication but does not eliminate the virus from the infected host. The persistence of a small pool of cells harboring integrated and replication-competent HIV genomes impedes viral eradication efforts. The HIV reservoir was originally described as a relatively homogeneous pool of resting memory CD4+ T cells. Over the past 20 years, the identification of multiple cellular subsets of CD4+ T cells endowed with distinct biological properties shed new lights on the heterogeneity of HIV reservoirs. It is now clear that HIV persists in a large variety of CD4+ T cells, which contribute to HIV persistence through different mechanisms. In this review, we summarize recent findings indicating that specific biological features of wellcharacterized subsets of CD4+ T cells individually contribute to the persistence of HIV. These include an increased sensitivity to HIV infection, specific tissue locations, enhanced survival and heightened capacity to proliferate. We also discuss the relative abilities of these cellular reservoirs to contribute to viral rebound upon ART interruption. Together, these findings reveal that the HIV reservoir is not homogeneous and should be viewed as a mosaic of multiple cell types that all contribute to HIV persistence through different mechanisms.