Figure 1

Cellular pathways of the establishment of HIV-1 latency in CD4 T-cells. (A) Generation of memory CD4 T-cells. Transcriptionally active CD4+CD8+ (double positive) thymocytes transition to a resting state upon completion of thymopoiesis to become resting naïve CD4 T-cells. Naïve cells are activated upon encounter with antigen-bearing dendritic cells and undergo rapid clonal expansion. A small fraction of activated CD4 T-cells survive and transition to a resting state, to become resting memory CD4 T-cells. (B) Infection during deactivation. Infection of an activated thymocyte can result in active integration or immediate silent integration. Latency can be established upon the transition to a naïve CD4 T-cell. Infection of an activated CD4 T-cell can result in active integration or immediate silent integration. Latency can be established upon the transition to a resting memory CD4 T-cell. Note that for immediate silent integration into an activated thymocyte or an activated CD4 T-cell, latency has already been established at the virological level. Due to the rapid deaths of activated cells, only cells which transition to a resting state represent clinically relevant latent infections. (C) Direct resting cell infection. Infection of a naïve CD4 T-cell, or of a resting memory CD4 T-cell, results in immediate silent integration, i.e., latency. Note that the relative contributions of the pathways shown here are not known.