Virus infection necessarily requires redirecting cellular resources towards viral progeny production. Adenovirus encodes the histone-like protein VII that causes catastrophic global reorganization of host chromatin to promote virus infection. Protein VII recruits the family of high mobility group box (HMGB) proteins to chromatin along with the histone chaperone SET. As a consequence of this recruitment, we find that protein VII causes chromatin-depletion of several linker histone H1 isoforms. The relationship between linker histone H1 and the functionally opposite HMGB proteins is critical for higher order chromatin structure. However, the physiological consequences of perturbing this relationship are largely unknown. Here, we employ complementary systems in Saccharomyces cerevisiae and human cells to demonstrate that adenovirus protein VII disrupts the H1-HMGB balance to obstruct the cell cycle. We find that protein VII causes an accumulation of G2/M cells both in yeast and human systems, underscoring the high conservation of this chromatin vulnerability. In contrast, adenovirus E1A and E1B proteins are well-established to override cell cycle regulation and promote transformation of human cells. Strikingly, we find that protein VII obstructs the cell cycle even in the presence of E1A and E1B, suggesting that protein VII-directed cell cycle disruption ensures host resources are directed towards viral proliferation during infection. Together, our results demonstrate that protein VII targets H1-HMGB1 antagonism to obstruct cell cycle progression, revealing an unexpected chromatin vulnerability exploited for viral benefit

中文翻译：

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病毒组蛋白样蛋白利用接头组蛋白和HMGB蛋白之间的拮抗作用阻碍细胞周期

病毒感染必然需要将细胞资源转向病毒后代的生产。腺病毒编码组蛋白样蛋白VII，后者导致宿主染色质发生灾难性的全局重组，从而促进病毒感染。Protein VII将高迁移率族盒（HMGB）蛋白家族与组蛋白伴侣SET一起募集到染色质中。作为这种募集的结果，我们发现蛋白质VII导致几种接头组蛋白H1同工型的染色质耗竭。接头组蛋白H1和功能相反的HMGB蛋白之间的关系对于高级染色质结构至关重要。然而，扰乱这种关系的生理后果在很大程度上是未知的。这里，我们在酿酒酵母和人细胞中采用互补系统，以证明腺病毒蛋白VII破坏H1-HMGB平衡以阻碍细胞周期。我们发现蛋白质VII导致酵母和人类系统中的G2 / M细胞积累，强调了这种染色质易损性的高度保守性。相比之下，腺病毒E1A和E1B蛋白已经建立，可以超越细胞周期调控并促进人类细胞转化。令人惊讶地，我们发现即使在E1A和E1B存在的情况下，蛋白VII也会阻塞细胞周期，这表明蛋白VII指导的细胞周期破坏可确保宿主资源在感染过程中直接针对病毒增殖。总之，我们的结果表明，蛋白VII靶向H1-HMGB1拮抗作用以阻止细胞周期进程，