Mechanisms of HIV latency: an emerging picture of complexity.
Rarely HIV type 1 establishes proviral latency within the host genome, maintained with little or no viral gene expression. This state has been quantitated in peripheral blood and lymphoid tissues of HIV-infected patients, appearing in the earliest days of infection. These rare cellular reservoirs are unaffected by current antiretroviral therapy and unrecognized by the host immune response, and can regenerate disseminated viremia if therapy is interrupted. Proviral latency may be established when a newly HIV-infected cell exits the cell cycle and returns to the resting state. Rarely, direct infection of resting cells may also occur. Multiple molecular mechanisms appear to underlie the establishment and maintenance of persistent, latent HIV infection, most frequent in the resting central memory CD4+ T cell. Interrupting processes that maintain latency may allow therapeutic attack of this primary form of persistent HIV infection, but a better understanding of relevant mechanisms in vivo is needed.
Margolis
David M
DM
Departments of Medicine, Microbiology and Immunology, and Epidemiology, University of North Carolina at Chapel Hill, 3302 Michael Hooker Research Center, CB#7435, Chapel Hill, NC, 27599-7435, USA. dmargo@med.unc.edu
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002843:Chromatin / Q000502:physiology; D016679:Genome, Viral; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D011533:Proviruses / Q000502:physiology; D012367:RNA, Viral / Q000502:physiology; D014158:Transcription, Genetic; D017735:Virus Latency / Q000187:drug effects / Q000502:physiology
D019380:Anti-HIV Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012367:RNA, Viral