Cellular Reservoirs of HIV-1 and their Role in Viral Persistence

摘要

A major obstacle in human immunodeficiency virus type 1 (HIV-1) eradication is the ability of the virus to remainnlatent in a subpopulation of the cells it infects. Latently infected cells can escape the viral immune response and persistnfor long periods of time, despite the presence of successful highly active antiretroviral therapy (HAART). Given thenappropriate stimulus, latently infected cells can reactivate and start producing infectious virions. The susceptibility ofnthese cell populations to HIV-1, their life span, their proliferative capacity, and their ability to periodically produce infectiousnvirus subsequent to alterations in cellular physiology and/or immunologic controls are critical issues which determinenthe contribution of these cells to viral persistence.nMemory CD4+ T cells due to the long life span, which may be several years, and their ability to reactivate upon encounternwith their cognate antigen or other stimulation, are considered a critical reservoir for maintenance of latent HIV-1 proviralnDNA. Cells of the monocyte-macrophage lineage, which originate in the bone marrow (BM), are of particular importancenin HIV-1 persistence due to their ability to cross the blood-brain barrier (BBB) and spread HIV-1 infection in the immunoprivilegedncentral nervous system (CNS). Hematopoietic progenitor cells (HPCs) are also a potential HIV-1 reservoir,nas several studies have shown that CD34+ HPCs carrying proviral DNA can be found in vivo in a subpopulation ofnHIV-1-infected patients. The ability of HPCs to proliferate and potentially generate clonal populations of infected cells ofnthe monocyte-macrophage lineage may be crucial in HIV-1 dissemination. The contribution of these and other cell populationsnin HIV-1 persistence, as well as the possible strategies to eliminate latently infected cells are critically examined innthis review.