乙型肝炎病毒
流式细胞术
生物
乙型肝炎
乙型肝炎表面抗原
体内
免疫系统
病毒学
分子生物学
病毒
免疫学
生物技术
作者
Caorui Lin,Lan Luo,Zhen Xun,Chenggong Zhu,Ying Huang,Yuchen Ye,Jiawei Zhang,Tianbin Chen,Songhang Wu,Fuguo Zhan,Bin Yang,Can Liu,Ning Ran,Caorui Lin
出处
期刊:Gut
[BMJ]
日期:2023-10-03
卷期号:73 (2): 338-349
标识
DOI:10.1136/gutjnl-2023-330389
摘要
Objective Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism. Design In total, 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, were recruited for this study. MOTS-c levels were measured by ELISA and its diagnostic value was evaluated by receiving operating characteristic curve analysis. The therapeutic effect of MOTS-c was observed in multiple HBV-infected mice and cells through various techniques, including transcriptomic sequencing, flow cytometry, immunofluorescence and electron microscopy. Additionally, MOTS-c’s potential interaction with myosin-9 (MYH9) and actin was predicted using immunoprecipitation, proteomics and target prediction software. Results MOTS-c negatively correlates with HBV DNA expression (R=−0.71), and its AUC (the area under the curve) for distinguishing CHB from healthy controls is 0.9530, and IA (immune reactive) from IC (inactive HBV carrier) is 0.8689. Inhibition of HBV replication (with a 50–70% inhibition rate) was observed alongside improved liver function without notable toxicity in vitro or in vivo. MOTS-c was found to promote mitochondrial biogenesis and enhance the MAVS (mitochondrial antiviral signalling protein) signalling pathway. The impact is dependent on MOTS-c’s ability to regulate MYH9-actin-mediated mitochondrial homeostasis. Conclusion MOTS-c has the potential to serve as a biomarker for the progression of HBV infection while also enhancing antiviral efficacy. These findings present a promising innovative approach for effectively treating patients with CHB. Furthermore, our research uncovers a novel role for MOTS-c in regulating MYH9-actin-mediated mitochondrial dynamics and contributing to mitochondrial biogenesis.
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