Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens.

中文翻译：

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流感病毒的表观遗传控制：H3K79甲基化在干扰素诱导的抗病毒反应中的作用。

流感病毒稳定了病毒-宿主功能相互作用的网络，这取决于染色质的动力学，并因此取决于表观遗传修饰。使用无偏搜索，我们分析了由感染引起的DNA甲基化和翻译后组蛋白修饰水平的表观遗传学变化。DNA甲基化未改变，而我们发现组蛋白乙酰化普遍下降，这与转录失活有关，并且可能与导致流感病毒感染的细胞转录损伤相配合。观察到H3K79甲基化的特别增加，使用特定的H3K79甲基化酶抑制剂，Dot1L酶或其沉默可增加流感病毒的复制。在Dot1L下调的条件下，抗病毒反应降低，因为检测到了NF-kB复合体和IFN-β，Mx1和ISG56表达的核易位降低。数据表明可以通过H3K79的甲基化来控制抗病毒信号传导，因此，在IFN途径受损的Dot1L抑制细胞中，流感病毒的复制不受影响。H3K79甲基化还控制了另一种有效的干扰素诱导病毒（如水泡性口炎病毒）的复制，但没有改变呼吸道合胞病毒的扩增，而后者不能很好地诱导干扰素的信号传导。H3K79的表观遗传甲基化可能在控制干扰素诱导的针对病毒病原体的信号传导中起重要作用。流感病毒复制在IFN途径受损的Dot1L抑制细胞中不受影响。H3K79甲基化还控制了另一种有效的干扰素诱导病毒（如水泡性口炎病毒）的复制，但没有改变呼吸道合胞病毒的扩增，而后者不能很好地诱导干扰素的信号传导。H3K79的表观遗传甲基化可能在控制干扰素诱导的针对病毒病原体的信号传导中起重要作用。流感病毒复制在IFN途径受损的Dot1L抑制细胞中不受影响。H3K79甲基化还控制了另一种有效的干扰素诱导病毒（如水泡性口炎病毒）的复制，但没有改变呼吸道合胞病毒的扩增，而后者不能很好地诱导干扰素的信号传导。H3K79的表观遗传甲基化可能在控制干扰素诱导的针对病毒病原体的信号传导中起重要作用。