Activity of novel drug candidates in primary cell models of HIV latency

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Linked publications, trials & patents

Abstract

Latently infected, quiescent CD4 T cells represent a central obstacle to eradication of HIV-1. Major hurdles are the low frequencies of latently infected cells in peripheral blood and the lack of known phenotypic markers that can distinguish them from uninfected ones. These impediments have prompted the development of in vitro cell models of latency. Such models allow manipulation of cellular and viral characteristics to gain a mechanistic understanding of how latency is established and regulated. However, no single experimental system of HIV latency is perceived to completely recapitulate the biology of the latent viral reservoir in vivo. This is mainly because (a) the mechanisms for establishment of latency by HIV are multiple; and (b) the types of cells harboring latent infection are also multiple. A wealth of knowledge has been gained regarding how specific stimuli (e.g. activation/differentiation, homeostatic proliferation, cytokines) and viral factors (e.g. integration site, Tat-driven expression) influence the dynamics of latent reservoirs in experimental systems. Project 2.2 will perform