γ-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication
γ-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication
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DOI：
10.1016/j.chom.2007.05.008
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发表时间：
2007-06-01
影响因子：
30.3
通讯作者：
Virgin, Herbert W., IV
中科院分区：
文献类型：
--
作者：
Tarakanova, Vera L.;Leung-Pinecla, Van;Virgin, Herbert W., IV
DNA病毒感染可引起宿主细胞的DNA损伤反应，包括ATM激酶激活和H2 AX磷酸化。这被认为是宿主细胞对复制病毒DNA的反应。与此相反，我们表明，在感染巨噬细胞鼠γ-疱疹病毒68（γ HV 68）积极诱导H2 AX磷酸化通过表达病毒激酶（orf 36）。γ HV 68编码的orf 36激酶及其EBV同系物BGLF 4独立于其它病毒基因诱导H2 AX磷酸化。该过程需要Orf 36的激酶结构域，并通过ATM增强。Orf 36对于感染动物中的γ HV 68复制是重要的，并且orf 36、H2 AX和ATM对于原代巨噬细胞中的γ HV 68有效复制都是关键的。因此，DNA损伤信号应答的近端组分的激活是有效的γ-疱疹病毒复制所需的主动病毒激酶驱动的策略。
DNA virus infection can elicit the DNA damage response in host cells, including ATM kinase activation and H2AX phosphorylation. This is considered to be the host cell response to replicating viral DNA. In contrast, we show that during infection of macrophages murine gamma-herpesvirus 68 (gamma HV68) actively induces H2AX phosphorylation by expressing a viral kinase (orf36). gamma HV68-encoded orf36 kinase and its EBV homolog, BGLF4, induce H2AX phosphorylation independently of other viral genes. The process requires the kinase domain of Orf36 and is enhanced by ATM. Orf36 is important for gamma HV68 replication in infected animals, and orf36, H2AX, and ATM are all critical for efficient gamma HV68 replication in primary macrophages. Thus, activation of proximal components of the DNA damage signaling response is an active viral kinase-driven strategy required for efficient gamma-herpesvirus replication.