Experimental approaches to the study of HIV-1 latency

Viral latency is a reversibly non-productive state of infection that allows some viruses to evade host immune responses. As a consequence of its tropism for activated CD4⁺ T cells, HIV-1 can establish latent infection in resting memory CD4⁺ T cells, which are generated when activated CD4⁺ T cells return to a quiescent state. Latent HIV-1 persists as a stably integrated but transcriptionally silent provirus. In this state, the virus is unaffected by immune responses or antiretroviral drugs, and this latent reservoir in resting CD4⁺ T cells is a major barrier to curing the infection. Unfortunately, there is no simple assay to measure the number of latently infected cells in a patient, nor is there an entirely representative in vitro model in which to explore the molecular mechanisms of latency. This Review will consider current approaches to the analysis of HIV-1 latency both in vivo and in vitro.