Fig. 1

HIV reservoir formation and dynamics. A The reservoir is established primarily in memory CD4⁺ T cells arising during the transition of infected effector cells to achieve immunological memory. Naïve cells become activated during HIV-1 infection due to HIV-1 itself and other antigenic stimuli. The resulting activated effector cells are ideal targets for productive HIV-1 infection. A large fraction of the infected effector cells will not survive, but an important subset become quiescent and transition to a memory cell phenotype, thereby silencing HIV-1. B The primary mechanism for reservoir persistence is due to the clonal expansion of partially activated latently infected cells due to homeostatic proliferation driven by IL-7 or antigen stimulation. Different viral clones reactivate and expand under different conditions, with some clones being reduced or eliminated due to viral cytopathic effects. The result is a gradual simplification of the clonal population as demonstrated by recurring integration site sequences (denoted in the figure by different colors for the proviruses)