Year: 2024
Type: article
Abstract: The mechanisms underlying the natural control of hepatitis B virus (HBV) infection have long been an intriguing question. Given the wide physiological range of liver stiffness and the growing attention to the role of mechanical microenvironment in homeostasis and diseases, we investigated how physical matrix cues impact HBV replication. High matrix stiffness significantly inhibited HBV replication and activated YAP in primary hepatocyte culture system, a key molecule in mechanosignaling. YAP activation notably suppressed HBV transcription and antigen expression. Several YAP-induced genes exhibited strong anti-HBV effects. Single-cell analysis of liver tissue from male individuals with active HBV replication revealed a strong significant negative correlation between YAP signature activation and HBV transcript levels. Intraperitoneal administration of YAP small molecule agonist potently controls HBV in male mouse models. These findings unveil a mechanism that involves the mechanical environment of hepatocytes and YAP to clear hepatotropic viral infection in the liver, providing new perspectives for HBV cure studies and antiviral development. The mechanisms of the natural control of hepatitis B virus infection remain obscured. Here, the authors reveal that matrix stiffness influences HBV replication via YAP-mediated mechanosignaling, uncovering a novel non-cytolytic mechanism for clearing viral infections in the liver.
Source: Nature Communications
Authors: Jianyu Ye, Fahong Li, Ting Hua, Kewei Ma, Jinyu Wang, Zixin Zhao, Zhongning Yang, Chen Luo, Ruohan Jia, Yaming Li, Menghan Hao, Jian Wu, Mengji Lu, Zhenghong Yuan, Jiming Zhang, Jieliang Chen
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
OpenAlex ID: W4402922844