Role of dendritic cells in exposing latent HIV-1 for the kill

Abstract

The development of effective yet nontoxic strategies to target the latent human immunodeficiency virus-1 (HIV-1) reservoir in antiretroviral therapy (ART)-suppressed individuals poses a critical barrier to a functional cure. The 'kick and kill' approach to HIV eradication entails proviral reactivation during ART, coupled with generation of cytotoxic T lymphocytes (CTLs) or other immune effectors equipped to eliminate exposed infected cells. Pharmacological latency reversal agents (LRAs) that have produced modest reductions in the latent reservoir ex vivo have not impacted levels of proviral DNA in HIV-infected individuals. An optimal cure strategy incorporates methods that facilitate sufficient antigen exposure on reactivated cells following the induction of proviral gene expression, as well as the elimination of infected targets by either polyfunctional HIV-specific CTLs or other immune-based strategies. Although conventional dendritic cells (DCs) have been used extensively for the purpose of inducing antigen-specific CTL responses in HIV-1 clinical trials, their immunotherapeutic potential as cellular LRAs has been largely ignored. In this review, we discuss the challenges associated with current HIV-1 eradication strategies, as well as the unharnessed potential of ex vivo-programmed DCs for both the 'kick and kill' of latent HIV-1.