Retroviral DNA Integration.

Retroviral DNA Integration.
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DOI:
10.1021/acs.chemrev.6b00125
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发表时间:
2016-10-26
期刊:
影响因子:
62.1
通讯作者:
Cherepanov, Peter
Cherepanov, Peter
中科院分区:
化学1区
文献类型:
--
作者:
Lesbats, Paul;Engelman, Alan N.;Cherepanov, Peter

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病毒RNA基因组的DNA拷贝整合到宿主染色质中是逆转录病毒复制的决定性步骤。该酶促过程由病毒编码的整合酶蛋白催化,该整合酶蛋白在逆转录病毒和LTR-逆转录转座子中是保守的。逆转录病毒整合通过两种整合酶活性进行:病毒DNA末端的3′-加工,然后将加工末端链转移到宿主细胞染色体DNA中。在此,我们回顾了逆转录病毒DNA整合的分子机制,重点是反应化学和结构的核蛋白复合物参与。我们还讨论了抗整合酶药物开发的最新进展,用于治疗艾滋病和整合逆转录病毒载体在基因治疗应用中的效用。
The integration of a DNA copy of the viral RNA genome into host chromatin is the defining step of retroviral replication. This enzymatic process is catalyzed by the virus-encoded integrase protein, which is conserved among retroviruses and LTR-retrotransposons. Retroviral integration proceeds via two integrase activities: 3′-processing of the viral DNA ends, followed by the strand transfer of the processed ends into host cell chromosomal DNA. Herein we review the molecular mechanism of retroviral DNA integration, with an emphasis on reaction chemistries and architectures of the nucleoprotein complexes involved. We additionally discuss the latest advances on anti-integrase drug development for the treatment of AIDS and the utility of integrating retroviral vectors in gene therapy applications.
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