Figure 2

Variation in the expression of proviruses integrated at the same position in different cells might be accounted for by a delayed mechanism leading to proviral silencing. Soon after infection the behavior of the provirus depends on the site of integration. (a) Integration into a chromosome position that is nonpermissive for gene expression results in a silent provirus. Note that although the environment may be nonpermissive for gene expression, the provirus itself need not be tightly repressed and is amenable to reactivation by various stimuli. (b) Integration into permissive chromatin permits viral gene expression. In HIV-1 this stage is prolonged because of the stability conferred by the Tat-TAR positive-feedback axis. (c) With time the provirus is silenced. At present, the trigger leading to the collapse of proviral activity is not known. (d) Once silenced, the provirus is tightly repressed and cannot be easily reactivated.