PLoS Pathogens | |
Epigenetic Regulation of HIV-1 Latency by Cytosine Methylation | |
Vicente Planelles1  Alberto Bosque2  Eric Verdin3  Annica Lindqvist3  Steven E. Kauder4  | |
[1] Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;Department of Medicine, University of California, San Francisco, California, United States of America;Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America;Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America | |
关键词: DNA methylation; HIV-1; T cells; Cytosine; DNA transcription; Viral replication; Polymerase chain reaction; Transcription factors; | |
DOI : 10.1371/journal.ppat.1000495 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
Human immunodeficiency virus type 1 (HIV-1) persists in a latent state within resting CD4+ T cells of infected persons treated with highly active antiretroviral therapy (HAART). This reservoir must be eliminated for the clearance of infection. Using a cDNA library screen, we have identified methyl-CpG binding domain protein 2 (MBD2) as a regulator of HIV-1 latency. Two CpG islands flank the HIV-1 transcription start site and are methylated in latently infected Jurkat cells and primary CD4+ T cells. MBD2 and histone deacetylase 2 (HDAC2) are found at one of these CpG islands during latency. Inhibition of cytosine methylation with 5-aza-2′deoxycytidine (aza-CdR) abrogates recruitment of MBD2 and HDAC2. Furthermore, aza-CdR potently synergizes with the NF-κB activators prostratin or TNF-α to reactivate latent HIV-1. These observations confirm that cytosine methylation and MBD2 are epigenetic regulators of HIV-1 latency. Clearance of HIV-1 from infected persons may be enhanced by inclusion of DNA methylation inhibitors, such as aza-CdR, and NF-κB activators into current antiviral therapies.
【 授权许可】
CC BY
【 预 览 】
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