Figure 4. Proposed role of PD-1 in the establishment and reversal of HIV latency.

(A) HIV preferentially infects activated CD4+ T cells which have been stimulated via T cell receptor engagement or a mitogen (red arrow). Following HIV integration, the productively infected cell (red box) usually dies by virus mediated cytolysis. Up-regulation of immune checkpoint markers such as PD-1, could potentially limit T-cell activation favouring latent over productive infection, where there is integration (green box) but no virus production. (B) Latently infected cells express immune checkpoint markers, including PD-1. The administration of anti-PD-1, or other immune checkpoint blockers, leads to activation of the T cells and increased expression of transcription factors that can enhance production of virus from latency. This leads to either immune mediated clearance or virus induced cell death.