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Suberoylanilide hydroxamic acid reactivates HIV from latently infected cellsContreras, Xavier ...Human immunodeficiency virus (HIV) persists in a latent form in infected individuals treated effectively with highly active antiretroviral therapy (HAART). In part, these latent proviruses account ... for the rebound in viral replication observed after treatment interruption. A major therapeutic challenge is to purge this reservoir. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) reactivates HIV from latency in chronically infected cell lines and primary cells. Indeed, P-TEFb, a criticaltranscription cofactor for HIV, is released and then recruited to the viral promoter upon stimulation with SAHA. The phosphatidylinositol 3-kinase/Akt pathway is involved in the initiation of these events. Using flowcytometry-based single cell analysis of protein phosphorylation, we demonstrate that SAHA activates this pathway in several subpopulations of T cells, including memory T cells that are the major viral reservoir in peripheral blood. Importantly, SAHA activates HIV replication in peripheral blood mononuclear cells from individuals treated effectively with HAART. Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans.Vir: The Journal of biological chemistry. - ISSN 0021-9258 (Vol. 284, issue 11, 2009, str. 6782-6789)Vrsta gradiva - članek, sestavni delLeto - 2009Jezik - angleškiCOBISS.SI-ID - 29183961
Avtor
Contreras, Xavier |
Schweneker, Marc |
Chen, Ching-Shih |
McCune, Joseph M |
Deeks, Steven G |
Martin, Jeffrey |
Peterlin, Matija Boris
Teme
Adult |
Hiv |
Immunology |
Metabolism |
Hiv Infections |
Drug Therapy |
Metabolism |
Hydroxamic Acids |
Pharmacokinetics |
Therapeutic Use |
Immunologic Memory |
Immunology |
Jurkat Cells |
Proviruses |
Immunology |
Metabolism |
T-Lymphocytes |
Immunology |
Metabolism |
Virology |
Virus Latency |
Immunology |
Drug Effects |
Virus Replication |
Drug Effects |
Immunology |
Limfociti T |
Odrasli |
Hidroksamske kisline |
HIV |
HIV infekcije |
Provirusi |
Imunski spomin |
Jurkat celice |
Virusna latenca |
Virus, podvojevanje
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Contreras, Xavier | ![]() |
Schweneker, Marc | ![]() |
Chen, Ching-Shih | ![]() |
McCune, Joseph M | ![]() |
Deeks, Steven G | ![]() |
Martin, Jeffrey | ![]() |
Peterlin, Matija Boris | 34721 |
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