During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication. Here, we examined effects of the DDR on several adenovirus serotypes. We demonstrate that wild-type Ad9 and Ad12 do not overcome MRN impairment. We also examined viral proteins involved in targeting MRN and found that unlike Ad5-E4orf3, expression of Ad9-E4orf3 is not sufficient for MRN mislocalization observed during infection. We conclude that adenovirus serotypes target MRN in distinct ways, and the MRN complex can impair DNA replication of wild-type viruses across the adenovirus family.

中文翻译：

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细胞型Mre11-Rad50-Nbs1复合体对野生型腺病毒的血清型特异性限制。

在细胞核中进行病毒复制期间，腺病毒的DNA基因组可与细胞DNA结合蛋白接触。人类5型腺病毒（Ad5）靶向细胞Mre11-Rad50-Nbs1复合体（MRN），以逃避DNA损伤反应（DDR）的检测。不能靶向MRN的Ad5突变体减少了病毒繁殖。先前的研究表明，多种腺病毒血清型与MRN的相互作用不同。尽管这些研究揭示了血清型之间多种多样的MRN相互作用，但仍不清楚这些差异如何影响病毒复制。在这里，我们检查了DDR对几种腺病毒血清型的影响。我们证明野生型Ad9和Ad12不能克服MRN损伤。我们还检查了与靶向MRN有关的病毒蛋白，发现与Ad5-E4orf3不同，Ad9-E4orf3的表达不足以感染期间观察到的MRN错位。我们得出的结论是，腺病毒血清型以不同的方式靶向MRN，而MRN复合物会损害整个腺病毒家族中野生型病毒的DNA复制。