Department of Infectious Disease, Qilu Hospital of Shandong University, 107# West Wenhua Road, Jinan, 250012, Shandong province, People's Republic of China.
Inflammation. 2019 Aug;42(4):1317-1325. doi: 10.1007/s10753-019-00992-5.
Type I interferon (IFN) response is central for host defense against viral infection. Tripartite motif 27 (TRIM27) is implicated in antiviral innate immune response; however, whether it affects the replication of hepatitis C virus (HCV) and the underlying mechanisms remain uncharacterized. Here, we show that TRIM27 expression is induced in Huh7.5 human hepatoma cells infected with HCV or stimulated with type I IFNs in vitro. In addition, TRIM27 overexpression increases and its knockdown decreases viral RNA and protein levels, suggesting that TRIM27 positively regulates HCV replication. Mechanistically, TRIM27 inhibits type I IFN response against HCV infection through inhibiting IRF3 and NF-κB pathways, since TRIM27 mutant unable to inhibit these two inflammatory pathways fails to promote HCV replication. Taken together, this study identifies TRIM27 as a novel positive regulator of HCV replication, and also implicates that targeting TRIM27 may serve as a therapeutic strategy for controlling HCV replication.
I 型干扰素（IFN）反应是宿主防御病毒感染的核心。三结构域蛋白 27（TRIM27）参与抗病毒先天免疫反应；然而，它是否影响丙型肝炎病毒（HCV）的复制及其潜在机制尚不清楚。在这里，我们表明 TRIM27 在感染 HCV 的 Huh7.5 人肝癌细胞或体外用 I 型 IFN 刺激时表达上调。此外，TRIM27 的过表达增加，其敲低减少病毒 RNA 和蛋白水平，表明 TRIM27 正向调节 HCV 复制。从机制上讲，TRIM27 通过抑制 IRF3 和 NF-κB 通路抑制 HCV 感染的 I 型 IFN 反应，因为不能抑制这两个炎症通路的 TRIM27 突变体不能促进 HCV 复制。总之，这项研究确定 TRIM27 是 HCV 复制的新型正调节剂，也暗示靶向 TRIM27 可能是控制 HCV 复制的治疗策略。
