Figure 1

Schematic representation of the most likely viral reservoir dynamics in vivo and the possible anti-reservoir drug strategies mentioned in the text. Briefly, latently infected cells proliferate by either homeostasis or antigen-driven activation. Part of the activated cells becomes productively infected, spreading the virus to uninfected cells, while another portion either dies or reverts to a latent state. These phenomena contribute to the expansion of the viral reservoir during lentiviral infections. If cell-to-cell viral spread is blocked by highly-intensified antiretroviral therapy (H-iART), activation-driven proliferation and homeostatic proliferation represent the main mechanisms for the expansion/persistence of the viral reservoir during therapy. One important component of H-iART, i.e. the CCR5 blocker maraviroc, was shown in a recent study (Ref. [8]) also to decrease activation-induced proliferation of the central and transitional memory T-cells (encompassing the viral reservoir). Antilatency drugs such as the histone deacetylase inhibitors may favor the transition of the activated latently infected cells to the productive class [vulnerable to viral cytopathogenicity, specific immune responses, or pro-oxidant drugs auch as buthionine sulfoximine (BSO)] at the expense of reversion of the same cells to the latent state. Finally, the gold salt auranofin, by decreasing the lifespan of the central and transitional memory T-cells, restricts their potential to expand by both homeostatic and activation-driven proliferation. Adapted and modified from Ref. [14].