A novel function for spumaretrovirus integrase: an early requirement for integrase-mediated cleavage of 2 LTR circles.
A novel function for spumaretrovirus integrase: an early requirement for integrase-mediated cleavage of 2 LTR circles.
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DOI：
10.1186/1742-4690-2-31
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发表时间：
2005-05-18
期刊：
影响因子：
3.3
通讯作者：
Sonigo P
中科院分区：
文献类型：
--
作者：
Delelis O;Petit C;Leh H;Mbemba G;Mouscadet JF;Sonigo P
逆转录病毒整合对于病毒持久性和发病机制、癌症以及宿主基因组进化至关重要。然而，目前尚不清楚为什么整合对于逆转录病毒的生产至关重要，特别是考虑到非整合病毒基因组的丰度和转录潜力。逆转录病毒核酸内切酶（也称为整合酶（IN））已被提议参与除整合之外的复制步骤，但通常被认为是辅助的。我们在此观察到，泡沫病毒家族逆转录病毒的整合主要取决于产生的病毒 DNA 的数量。此外，我们发现 IN 通过特异性切割 LTR-LTR 连接处的保守回文序列，直接参与 2-LTR 环的线性 DNA 生产。这些结果挑战了整合酶的基本功能是催化逆转录病毒 DNA 整合的普遍观点。通过控制线性 DNA 的产生，该步骤上游的整合酶活性足以解释对该酶的绝对需求。 IN 在 2-LTR 环连接上的新作用解释了在感染 IN 突变体的细胞中观察到的多效性效应。这可以解释为什么1）携带缺陷IN的突变体体内2-LTR环积累，而其线性和整合的DNA池减少； 2) 为什么以一致的方式处理两个 LTR。它还解决了有关泡沫逆转录病毒整合的原始难题。更一般地说，它建议重新评估 2-LTR 环作为逆转录病毒循环中的功能中间体，并重新考虑整合原病毒的形成是逆转录病毒生产的重要步骤的想法。
Retroviral integration is central to viral persistence and pathogenesis, cancer as well as host genome evolution. However, it is unclear why integration appears essential for retrovirus production, especially given the abundance and transcriptional potential of non-integrated viral genomes. The involvement of retroviral endonuclease, also called integrase (IN), in replication steps apart from integration has been proposed, but is usually considered to be accessory. We observe here that integration of a retrovirus from the spumavirus family depends mainly on the quantity of viral DNA produced. Moreover, we found that IN directly participates to linear DNA production from 2-LTR circles by specifically cleaving the conserved palindromic sequence found at LTR-LTR junctions. These results challenge the prevailing view that integrase essential function is to catalyze retroviral DNA integration. Integrase activity upstream of this step, by controlling linear DNA production, is sufficient to explain the absolute requirement for this enzyme. The novel role of IN over 2-LTR circle junctions accounts for the pleiotropic effects observed in cells infected with IN mutants. It may explain why 1) 2-LTR circles accumulate in vivo in mutants carrying a defective IN while their linear and integrated DNA pools decrease; 2) why both LTRs are processed in a concerted manner. It also resolves the original puzzle concerning the integration of spumaretroviruses. More generally, it suggests to reassess 2-LTR circles as functional intermediates in the retrovirus cycle and to reconsider the idea that formation of the integrated provirus is an essential step of retrovirus production.
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影响因子：
5.4
作者：
COBRINIK, D;KATZ, R;LEIS, J
通讯作者：
LEIS, J
DOI：
10.1073/pnas.81.20.6461
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DONEHOWER, LA;VARMUS, HE
通讯作者：
VARMUS, HE
DOI：
10.1073/pnas.86.8.2525
发表时间：
1989-04-01
影响因子：
11.1
作者：
BROWN, PO;BOWERMAN, B;BISHOP, JM
通讯作者：
BISHOP, JM
影响因子：
5.4
作者：
Delelis, O;Saïb, A;Sonigo, P
通讯作者：
Sonigo, P
影响因子：
5.4
作者：
ENGELMAN, A;CRAIGIE, R
通讯作者：
CRAIGIE, R