Integrase and integration: biochemical activities of HIV-1 integrase.

Integrase and integration: biochemical activities of HIV-1 integrase.
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整合酶和整合:HIV-1整合酶的生化活性。

DOI:
10.1186/1742-4690-5-114
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发表时间:
2008-12-17
期刊:
影响因子:
3.3
通讯作者:
Mouscadet JF
Mouscadet JF
中科院分区:
医学2区
文献类型:
--
作者:
Delelis O;Carayon K;Saïb A;Deprez E;Mouscadet JF

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逆转录病毒DNA的整合是逆转录病毒复制的必要步骤,因为前病毒DNA是生产性感染的模板。整合酶,一种逆转录病毒酶,催化整合。整合的过程可以分为两个连续的反应。第一种称为3 '-加工,对应于特异性核酸内切反应,其制备病毒DNA末端,以使其能够通过酯交换反应共价插入宿主细胞基因组中,称为链转移。最近,我们的小组在体外报道了全长整合酶对两种逆转录病毒整合酶(HIV-1和PFV-1)的新的比活性。这种内部切割的活性发生在特定的回文序列处,该回文序列模拟描述为2-LTR环的LTR-LTR连接,2-LTR环是在病毒感染期间发现的特有病毒DNA形式。此外,最近的研究表明,存在一个弱的回文共识发现在整合位点。总之,这些数据强调了逆转录病毒整合酶结合对称序列的倾向,并给出了用于基因治疗的靶向特定序列的前景。
Integration of retroviral DNA is an obligatory step of retrovirus replication because proviral DNA is the template for productive infection. Integrase, a retroviral enzyme, catalyses integration. The process of integration can be divided into two sequential reactions. The first one, named 3'-processing, corresponds to a specific endonucleolytic reaction which prepares the viral DNA extremities to be competent for the subsequent covalent insertion, named strand transfer, into the host cell genome by a trans-esterification reaction. Recently, a novel specific activity of the full length integrase was reported, in vitro, by our group for two retroviral integrases (HIV-1 and PFV-1). This activity of internal cleavage occurs at a specific palindromic sequence mimicking the LTR-LTR junction described into the 2-LTR circles which are peculiar viral DNA forms found during viral infection. Moreover, recent studies demonstrated the existence of a weak palindromic consensus found at the integration sites. Taken together, these data underline the propensity of retroviral integrases for binding symmetrical sequences and give perspectives for targeting specific sequences used for gene therapy.
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影响因子: 4.8
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