Recent progress in understanding HIV reservoirs.

Abstract

Reservoirs of HIV-1-infected cells persist long-term despite highly effective antiretroviral suppression therapy and represent the main barrier against a cure for HIV-1. This review summarizes recent advances in understanding the complexity and diversity of viral reservoir cells. Latently infected memory CD4 T cells are the predominant cell compartment responsible for viral persistence, but some studies suggest that myeloid cells, and possibly hematopoietic progenitors, can also serve as long-term viral reservoirs. Specific phenotypic markers, including T-cell activation and exhaustion molecules, may denote CD4 T cells enriched for replication-competent proviruses. Clonal proliferation of infected CD4 T cells in vivo represents an important mechanism responsible for the remarkable long-term stability of the viral reservoir. Multiple new assays, including near full-genome proviral sequencing and simplified versions of viral outgrowth assays, are being developed to analyze and quantify persisting reservoirs of HIV-1-infected cells. Recent technological advances allow to profile the molecular structure and composition of viral reservoir cells in great detail. Continuous progress in understanding phenotypic and functional properties of viral reservoir cells provides clues for novel clinical interventions to destabilize viral persistence during antiretroviral therapy.