Lesbats Paul, Engelman Alan N, Cherepanov Peter
Clare Hall Laboratories, The Francis Crick Institute , Blanche Lane, South Mimms, EN6 3LD, U.K.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School , 450 Brookline Avenue, Boston, Massachusetts 02215 United States.
Chem Rev. 2016 Oct 26;116(20):12730-12757. doi: 10.1021/acs.chemrev.6b00125. Epub 2016 May 20.
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.
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。这个酶促过程由病毒编码的整合酶蛋白催化，该蛋白在逆转录病毒和LTR逆转座子中保守。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，随后是加工后的末端链转移到宿主细胞染色体DNA中。在此，我们综述逆转录病毒DNA整合的分子机制，重点关注所涉及的核蛋白复合物的反应化学和结构。我们还讨论了用于治疗艾滋病的抗整合酶药物开发的最新进展以及整合逆转录病毒载体在基因治疗应用中的效用。
