Effect of DNA repair protein Rad18 on viral infection.
Effect of DNA repair protein Rad18 on viral infection.
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DOI：
10.1371/journal.ppat.0020040
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发表时间：
2006-05
期刊：
影响因子：
6.7
通讯作者：
Mulder LC
中科院分区：
文献类型：
--
作者：
Lloyd AG;Tateishi S;Bieniasz PD;Muesing MA;Yamaizumi M;Mulder LC
属于DNA修复机制的宿主因子被认为在整合的强制性步骤中帮助逆转录病毒。在这里，我们描述了DNA修复分子Rad 18，复制后修复途径的一个组成部分，对病毒感染的影响。与我们的预期相反，与Rad 18 +/+对照相比，缺乏Rad 18的细胞始终更容易进行病毒转导。值得注意的是，这种易感性是整合独立的，因为缺乏整合活性的逆转录病毒也显示出感染的初始步骤的增强。此外，还观察到Rad 18 −/−细胞对腺病毒的敏感性升高。这些数据表明，Rad 18以非特异性方式抑制病毒感染，可能是通过靶向进入的DNA。此外，考虑到最近发表的数据，似乎DNA修复成分与传入病毒之间的相互作用通常会抑制感染，而不是合作建立感染。各种细胞因子被认为与入侵的逆转录病毒相互作用，要么协助病毒蛋白质，要么作为保护因子对抗它们。因此，有效的病毒感染取决于这两组相反分子之间的平衡方式。作者发现，Rad 18是复制后DNA修复途径的一个组成部分，它不是帮助逆转录病毒感染，而是抑制其建立，干扰入侵DNA的积累。他们还发现，这种抑制活性不仅限于逆转录病毒，还涉及腺病毒感染。这些结果与最近发表的结果相结合，导致作者假设DNA修复介导的基因组稳定性维持在病毒感染中的作用，或者换句话说，病毒入侵也是基因组稳定性的问题。
Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18+/+ controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18−/− cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment. Various cellular factors are thought to interact with invading retroviruses, either assisting the viral proteins or functioning as protecting factors against them. Productive viral infection, therefore, depends on the way the equilibrium between these two opposite group of molecules is leaning. The authors find that Rad18, a component of the post-replication DNA repair pathway, instead of aiding retroviral infection suppresses its establishment, interfering with the accumulation of the invading DNA. They also find that such suppressive activity is not restricted only to retroviruses but also concerns adenovirus infection. These results, in conjunction with those recently published, lead the authors to hypothesize a role for DNA repair mediated genome stability maintenance in viral infection, or in other words, that viral invasion is also a matter of genome stability.