Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.
Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
Sci Rep. 2020 Nov 27;10(1):20763. doi: 10.1038/s41598-020-77166-z.
Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1β reduced the level of HBV RNA. However, the mechanism underlying IL-1β-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1β, suggesting that MCPIP1 is required for IL-1β-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1β.
乙型肝炎病毒 (HBV) 是慢性病毒性肝炎、肝硬化和肝细胞癌的主要致病因素。我们之前证明，促炎细胞因子白细胞介素-1β (IL-1β) 降低了 HBV RNA 的水平。然而，IL-1β介导的病毒 RNA 减少的机制尚不完全清楚。在这项研究中，我们报告免疫调节剂单核细胞趋化蛋白-1 诱导蛋白 1 (MCPIP1) 可以降低肝细胞中的 HBV RNA。HBV 感染患者和小鼠的肝组织中 MCPIP1 的表达水平更高。MCPIP1 的过表达降低了 HBV RNA，而体外敲除 MCPIP1 则增强了 HBV 的产生。MCPIP1 介导的病毒 RNA 减少需要 RNA 酶活性或寡聚化的结构域。HBV RNA 的 epsilon 结构对于其抗病毒活性很重要，并且在无细胞系统中被 MCPIP1 切割。最后，敲除 MCPIP1 减弱了 IL-1β 的抗 HBV 作用，表明 MCPIP1 是 IL-1β 介导的 HBV RNA 减少所必需的。总的来说，这些结果表明 MCPIP1 可能参与了 IL-1β 下游的抗病毒作用。
