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 (gammaHV68) actively induces H2AX phosphorylation by expressing a viral kinase (orf36). GammaHV68-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 gammaHV68 replication in infected animals, and orf36, H2AX, and ATM are all critical for efficient gammaHV68 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.

中文翻译：

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γ-疱疹病毒激酶通过诱导 H2AX 磷酸化来促进病毒复制，从而主动启动 DNA 损伤反应。

DNA 病毒感染可引发宿主细胞中的 DNA 损伤反应，包括 ATM 激酶激活和 H2AX 磷酸化。这被认为是宿主细胞对复制病毒 DNA 的反应。相比之下，我们显示在巨噬细胞感染期间鼠 γ-疱疹病毒 68 (gammaHV68) 通过表达病毒激酶 (orf36) 积极诱导 H2AX 磷酸化。GammaHV68 编码的 orf36 激酶及其 EBV 同源物 BGLF4 独立于其他病毒基因诱导 H2AX 磷酸化。该过程需要 Orf36 的激酶结构域，并由 ATM 增强。Orf36 对于受感染动物中的 gammaHV68 复制很重要，而 orf36、H2AX 和 ATM 对原代巨噬细胞中 gammaHV68 的有效复制都至关重要。因此，