期刊
VIROLOGY
卷 440, 期 2, 页码 182-189出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.02.022
关键词
HIV-1 latency; Integration site; CpG methylation; H3K9 methylation; GLP
类别
资金
- National Grand Program on Key Infectious Disease [2012ZX10001003]
- National Natural Science Funding of China [31171247]
Understanding the mechanism of HIV-1 latency is crucial to eradication of the viral reservoir in HIV-1-infected individuals. However, the role of histone methyltransferase (HMT) G9a-like protein (GLP) in HIV-1 latency is still unclear. In the present work, we established four clonal cell lines containing HIV-1 vector. We found that the integration sites of most clonal cell lines favored active gene regions. However, we also observed hypomethylation of CpG of HIV 5'LTR in all four clonal cell lines. Additionally, 5'-deoxy-5'-methylthioadenosine (MTA), a broad-spectrum histone methyltransferase inhibitor, was used to examine the role of histone methylation in HIV-1 latency. MTA was found to decrease the level of H3K9 dimethylation, causing reactivation of latent HIV-1 in C11 cells. GLP knockdown by small interfering RNA clearly induced HIV-1 LTR expression. Results suggest that GLP may play a significant role in the maintenance of HIV-1 latency by catalyzing dimethylation of H3K9. (C) 2013 Elsevier Inc. All rights reserved.
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