title: Didehydro-Cortistatin A: a new player in HIV-therapy?
abstract: Antiretroviral therapy can effectively suppress HIV-1 infection but is ineffective against integrated proviruses. A latent viral reservoir composed of latently infected CD4(+)T cells persists under suppressive therapy, and infected individuals must remain indefinitely on antiretroviral therapy to prevent viral reactivation and propagation. Despite therapy, some degree of low-level ongoing replication is detected and transient viral reactivation may replenish the latent reservoir. An analog of the natural compound, Cortistatin A, blocks HIV-1 transcription by specifically targeting the viral transactivator, Tat. Treatment of latently infected cells with this Tat inhibitor promotes a state of deep-latency from which HIV reactivation capacity is greatly diminished. Here we discuss the use of Tat inhibitors to limit the latent reservoir to achieve a functional cure.
authors.affiliation: a Department of Immunology and Microbial Science , The Scripps Research Institute , Jupiter , FL , USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mousseau
authors.affiliation: a Department of Immunology and Microbial Science , The Scripps Research Institute , Jupiter , FL , USA.
authors.forename: Susana T
authors.initials: ST
authors.lastname: Valente
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D007546:Isoquinolines / Q000627:therapeutic use*; D017735:Virus Latency / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C576992:didehydro-cortistatin A; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: HIV latency; HIV transcription; Tat inhibitor; antiretroviral therapy; deep-latency; didehydro-Cortistatin A; functional cure; latent reservoir; viral reactivation