Peering into the HIV reservoir

Abstract

The main obstacle to HIV eradication is the establishment of a long-term persistent HIV reservoir. Although several therapeutic approaches have been developed to reduce and eventually eliminate the HIV reservoir, only a few have achieved promising results. A better knowledge of the mechanisms involved in the establishment and maintenance of HIV reservoir is of utmost relevance for the design of new therapeutic strategies aimed at purging it with the ultimate goal of achieving HIV eradication or alternatively a functional cure. In this regard, it is also important to take a close look into the cellular HIV reservoirs other than resting memory CD4 T-cells with key roles in reservoir maintenance that have been recently described. Unraveling the special characteristics of these HIV cellular compartments could aid us in designing new therapeutic strategies to deplete the latent HIV reservoir.

Keywords: HIV reservoir; T follicular helper cells; myeloid-derived cells; resting memory CD4 T cells; stem cell-like memory T cells.

Figure 1. Main cellular compartments of HIV reservoir

Different cell populations of CD4 T cells contribute in a specific way to maintain the viral reservoir. A) Resting memory CD4+ T cells have been considered the major cellular reservoir of quiescent but replication-competent viruses. B) T helper follicular cells have been defined as the main memory CD4+ T cell compartment supporting infection, replication, and production of HIV. C) Stem cell-like memory T cells have been proposed as the most stable and permanent component of the latent HIV reservoir.

Figure 2. Barriers to CTL-mediated HIV eradication

The figure show the main barriers encountered by HIV-specific CTL response to eliminate HIV-infected cells. A) Escape Mutations: the high ability of HIV to generate escape mutations in epitopes recognized by CTLs. B) T-cell Exhaustion: HIV-induced exhaustion of CTLs renders them unable to eliminate HIV-infected cells. C) Compartimentalization: anatomical compartimentalization in the germinal center of lymph nodes that impedes access of CTLs in the T-cell zone to HIV-infected cells in the B-cell follicle. D) Latent Infection: the establishment of a pool of latently infected T cells that do not express HIV epitopes and thus cannot be recognized by CTLs.