Latency: the hidden HIV-1 challenge.
Eradication of HIV-1 from an infected individual cannot be achieved by current regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time and are able to replenish systemic infection upon interruption of the treatment. Therapeutic targeting of viral latency will require a better understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 in resting memory CD4 T cells, the most prominent reservoir of transcriptionally silent provirus. Since the molecular mechanisms that permit long term transcriptional control of proviral gene expression in these cells are still obscure, this review aims at summarizing the various aspects of the problem that need to be considered. In particular, this review will focus the attention on the control of transcription imposed by chromatin through various epigenetic mechanisms. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication.
Marcello
Alessandro
A
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99 - 34012 Trieste, Italy. marcello@icgeb.org
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002843:Chromatin / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D011533:Proviruses / Q000235:genetics; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication
D019380:Anti-HIV Agents; D002843:Chromatin; D012367:RNA, Viral