Long-lived reservoirs of HIV-1

Abstract

HIV-1 persistence in long-lived cellular reservoirs remains a major barrier to a cure. In a recent Nature Medicine paper, Buzon et al. identify memory T cells with stem cell-like properties (TSCM) that harbor infectious provirus and that likely contribute to HIV-1 persistence.

Figure 1

HIV transmission among potential long-lived cellular reservoirs. Cartoon illustration depicting two pathways by which cells that express the HIV-1 receptors (CD4 and CXCR4 or CCR5) can acquire integrated provirus. In untreated people, virions directly infect a target cell and the error prone reverse transcriptase incorporates approximately one mutation per viral genome per replication cycle. In treated people, drugs can effectively prevent new infection. However, it has been hypothesized that integrated provirus may spread by cell division and differentiation of precursor cells. A proviral genome acquired by cellular replication will have the same sequence and integration site as the parent cell. In optimally treated people, cellular reservoirs are expected to decay over time according to the life span of the cell type that harbors them. Buzon et al. observed a significant decrease in the amount of HIV DNA associated with T_EM and T_TD but not T_NA, T_CM or T_SCM over 7–11 years of continuous treatment [5]. Abbreviations: HSPC, hematopoietic stem and progenitor cells (CD133⁺ HSPCs are a heterogeneous population of precursor cells that include hematopoietic stem cells.); T_NA, naïve CD4⁺ T lymphocyte; T_SCM, stem cell memory CD4⁺ T lymphocyte; T_CM, central memory CD4⁺ T lymphocyte; T_EM, effector memory CD4⁺ T lymphocyte; T_TD, terminally differentiated CD4⁺ T lymphocyte. Cell types with a greater potential to self-renew and differentiate are indicated by the dashed circular arrow.