Anti-viral opportunities during transcriptional activation of latent HIV in the host chromatin.
Human immunodeficiency virus (HIV) when integrated into a host chromosome exists in a transcriptionally inactive but replication-competent state. Such latent infection represents a major challenge to HIV eradication efforts because a permanent virus reservoir resided in the infected cell is able to spike the viral load on immune suppression or during interruption of highly active anti-retroviral therapy. Understanding the molecular mechanisms that control HIV proviral latency and its reactivation could provide new perspectives on host factors as therapeutic targets for abolishing cellular reservoirs of dormant HIV. Although the control of HIV latency is multifactorial, chromatin structure and the chromatin-associated transcriptional machinery are known to be important factors. For instance, transcription initiation of the HIV provirus involves a complex molecular interplay between chromatin-associated proteins and the virus-encoded trans-activator, Tat. The first part of this review discusses our current understanding of the elements involved in HIV transcriptional activation and viral mRNA elongation, mainly post-translational modifications of HIV Tat and its interactions with host chromatin-modifying enzymes and chromatin-remodeling complexes. The second part highlights new experimental therapeutic approaches aimed at administrating activators of HIV gene expression to reduce or eliminate the pool of latently HIV-infected cells.
Mujtaba
Shiraz
S
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1677, New York, NY 10029, USA.
Zhou
Ming-Ming
MM
D000107:Acetylation; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods; D015533:Transcriptional Activation; D016662:Virus Integration; D017735:Virus Latency; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D019380:Anti-HIV Agents; D002843:Chromatin; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor