The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription
The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription
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MOV10解旋酶通过抑制病毒逆转录来限制乙型肝炎病毒复制
DOI：
10.1074/jbc.ra119.009435
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发表时间：
2019-12-20
影响因子：
4.8
通讯作者：
Zhang, Quan
中科院分区：
文献类型：
--
作者：
Liu, Tingting;Sun, Qingsong;Zhang, Quan
干扰素通过诱导抗病毒蛋白表达来抑制病毒。人莫洛尼白血病病毒 10 (MOV10) 是一种干扰素诱导的抗病毒蛋白，它是一种超家族 1 RNA 解旋酶，已被证明可以抑制逆转录病毒和多种 RNA 病毒。然而，MOV10 是否也抑制 DNA 病毒，包括乙型肝炎病毒 (HBV)，目前尚未确定。在这里，我们报告 MOV10 显着降低细胞内 HBV DNA 的水平，从而显着抑制 HBV 实验株和临床分离株。机制实验表明，MOV10 与 HBV RNA 相互作用，阻断病毒逆转录的早期步骤，从而损害病毒 DNA 合成，而不影响病毒基因表达和前基因组 RNA 衣壳化。此外，MOV10解旋酶结构域的突变导致与HBV RNA的结合以及抗HBV活性的丧失。总之，我们的结果表明 MOV10 限制 HBV 复制，这一见解可能为抗 HBV 疗法的开发开辟新途径。
Interferons inhibit viruses by inducing antiviral protein expression. One of the interferon-induced antiviral proteins, human Moloney leukemia virus 10 (MOV10), a superfamily 1 RNA helicase, has been shown to inhibit retroviruses and several RNA viruses. However, it remains undetermined whether MOV10 also inhibits DNA viruses, including hepatitis B virus (HBV). Here, we report that MOV10 dramatically reduces the levels of intracellular HBV DNA, resulting in significant inhibition of both the HBV experimental strain and the clinical isolates. Mechanistic experiments revealed that MOV10 interacts with HBV RNA and blocks the early step of viral reverse transcription, thereby impairing viral DNA synthesis, without affecting viral gene expression and pregenomic RNA encapsidation. Moreover, mutation of the helicase domain of MOV10 caused loss of binding to HBV RNA and of the anti-HBV activity. Together, our results indicate that MOV10 restricts HBV replication, insights that may open new avenues to the development of anti-HBV therapeutics.