HIV reservoirs and latency models

Abstract

The main impediment to a cure for HIV is the existence of long-lasting treatment resistant viral reservoirs. In this review, we discuss what is currently known about reservoirs, including their formation and maintenance, while focusing on latently infected CD4+ T cells. In addition, we compare several different in vivo and in vitro models of latency. We comment on how each model may reflect the properties of reservoirs in vivo, especially with regard to cell phenotype, since recent studies demonstrate that multiple CD4+ T cell subsets contribute to HIV reservoirs and that with HAART and disease progression the relative contribution of different subsets may change. Finally, we focus on the direct infection of resting CD4+ T cells as a source of reservoir formation and as a model of latency, since recent results help explain the misconception that resting CD4+ T cells appeared to be resistant to HIV in vitro.

Figure 1. Continuum of Latency

Several types of post-integration latency may exist. Some latently infected cells may contain integrated DNA without transcribing viral RNA (top). Other cells may transcribe viral RNA, but not may translate viral proteins (second from top). Finally, some latent cells may produce viral proteins but not infectious virions (second from bottom). Cells are no longer latent when they produce virions, as is the case in activated CD4+T cells (bottom).