State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Institutes of Liver Diseases Research of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.
The Key Laboratory of Molecular Pathology (Hepatic Diseases) of Guangxi, Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Aliment Pharmacol Ther. 2022 Sep;56(5):878-889. doi: 10.1111/apt.17124. Epub 2022 Jul 24.
Hepatitis B virus (HBV) infection is a serious global health burden. TRIM26 has been reported to affect hepatitis C virus replication.
To manifest the role of TRIM26 on HBV replication and explore if there are single-nucleotide polymorphisms (SNPs) in TRIM26 associated with response to pegylated interferon-alpha (PegIFNα) treatment in patients with chronic hepatitis B (CHB).
We investigated the effect and mechanism of TRIM26 on HBV replication in vitro. The association between SNPs in TRIM26 and PegIFNα treatment response was evaluated in two independent cohorts including 238 and 707 patients with HBeAg-positive CHB.
Knockdown of TRIM26 increased, while overexpression of TRIM26 inhibited, HBV replication. Co-immunoprecipitation assays and immunofluorescence showed that TRIM26 interacted and co-localised with HBx. Co-transfection of HBx-HIS and TRIM26-FLAG plasmids in Huh7 cells showed that TRIM26 inhibited the expression of HBx. Furthermore, TRIM26 inhibited HBV replication by mediating HBx ubiquitination degradation, and TRIM26 SPRY domain was responsible for the interaction and degradation of HBx. Besides, IFN increased TRIM26 expression. TRIM26 rs116806878 was associated with response to PegIFNα in two CHB cohorts. Moreover, a polygenic score integrating TRIM26 rs116806878, STAT4 rs7574865 and CFB rs12614 (previously reported to be associated with response to PegIFNα) was related to response to PegIFNα in CHB.
TRIM26 inhibits HBV replication; IFN promotes TRIM26 expression. TRIM26 exerts an inhibitory effect on HBx by promoting ubiquitin-mediated degradation of HBx. Furthermore, TRIM26 rs116806878 is a potential predictive biomarker of response to PegIFNα in patients with CHB.
乙型肝炎病毒（HBV）感染是一个严重的全球健康负担。TRIM26 已被报道影响丙型肝炎病毒的复制。
揭示 TRIM26 对 HBV 复制的作用，并探讨 TRIM26 中的单核苷酸多态性（SNP）是否与慢性乙型肝炎（CHB）患者对聚乙二醇干扰素-α（PegIFNα）治疗的反应相关。
我们在体外研究了 TRIM26 对 HBV 复制的影响及其机制。在包括 238 例和 707 例 HBeAg 阳性 CHB 患者的两个独立队列中，评估了 TRIM26 中的 SNP 与 PegIFNα 治疗反应的相关性。
TRIM26 的敲低增加，而过表达则抑制 HBV 复制。免疫共沉淀和免疫荧光显示 TRIM26 与 HBx 相互作用并共定位。在 Huh7 细胞中转染 HBx-HIS 和 TRIM26-FLAG 质粒显示，TRIM26 抑制 HBx 的表达。此外，TRIM26 通过介导 HBx 泛素化降解来抑制 HBV 复制，TRIM26 的 SPRY 结构域负责 HBx 的相互作用和降解。此外，IFN 增加了 TRIM26 的表达。TRIM26 rs116806878 与两个 CHB 队列中对 PegIFNα 的反应相关。此外，整合了 TRIM26 rs116806878、STAT4 rs7574865 和 CFB rs12614（先前报道与 PegIFNα 的反应相关）的多基因评分与 CHB 对 PegIFNα 的反应相关。
TRIM26 抑制 HBV 复制；IFN 促进 TRIM26 的表达。TRIM26 通过促进 HBx 的泛素化降解对 HBx 发挥抑制作用。此外，TRIM26 rs116806878 是 CHB 患者对 PegIFNα 反应的潜在预测生物标志物。
