A new chimeric protein represses HIV-1 LTR-mediated expression by DNA methylase

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• 作者：Alberto Martinez-Colom^a ; ^b ; Sandra Lasarte^a ; ^b ; Alejandra Ferná ; ndez-Pineda^a ; ^b ; Miguel Relloso^a ; ^b ; Maria Angeles Mu&ntilde ; oz-Ferná ; ndez^a ; ^b ; ^c ; ^{mmunoz.hgugm@salud.madrid.org} ; ^{mmunoz.hgugm@gmail.com}
• 关键词：HIV-1 ; DNA methyltransferases ; LTRs ; DNMT3b ; IN3b chimeric protein
• 刊名：Antiviral Research
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：98
• 期：3
• 页码：394-400
• 全文大小：1239 K

文摘

Once the human immunodeficiency virus (HIV) genome is inserted into the host genome, the virus cannot be removed, which results in latency periods and makes it difficult to eradicate. The majority of strategies to eradicate HIV have been based on preventing virus latency, thereby enabling antiretroviral drugs to act against HIV replication. Another innovative strategy is permanently silencing the integrated virus to prevent the spread of infection. Epigenetic processes are natural mechanisms that can silence viral replication. We describe a new chimeric protein (IN3b) that consists of a HIV-1 integrase domain, which recognises the HIV long terminal repeat (LTR) and the catalytic domain of DNA methyltransferase DNMT3b. Our objective was to silence HIV replication by the specific delivery of the catalytic methyltransferase domain to the LTR promoter to induce its methylation. We found that our IN3b chimeric protein was expressed in the nucleus and decreased LTR-associated HIV genome expression and HIV replication. Therefore, the IN3b chimeric protein may be an effective tool against HIV replication and maybe used in a new line of research to induce or maintain HIV latency.