Work

Inhibition of STING alleviates lipotoxicity in viral-infected primary mouse hepatocytes and viral hepatitis-associated liver damage

Year: 2026

Type: article

Abstract: Introduction: RNA virus infections often cause liver steatosis and lipid deposition, which significantly exacerbate liver damage. However, the underlying mechanisms linking viral-induced lipid accumulation to hepatocellular death remain incompletely understood. Methods: We employed a primary mouse hepatocyte model of vesicular stomatitis virus (VSV) infection and an in vivo mouse model of virus-induced acute liver failure. The role of STING was investigated through genetic knockdown and pharmacological inhibition using H-151. Furthermore, clinical relevance was assessed using data from the National Health and Nutrition Examination Survey (NHANES, 2007-2010) to analyze correlations between hepatic steatosis and injury biomarkers. Results: Viral exposure induced time-dependent upregulation and activation of STING, which driven the pathological accumulation of lipid droplets and subsequent ferroptotic cell death. Genetic knockdown or pharmacological inhibition of STING (H-151) effectively mitigated metabolic stress and preserved cell viability. These protective effects were recapitulated in vivo, where H-151 administration significantly improved survival and reduced tissue damage in a mouse model of virus-induced acute liver failure. Analysis of NHANES data corroborated these findings, showing that in patients with concurrent viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD), the fatty liver index (FLI) and triglyceride levels correlate linearly with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Conclusion: Collectively, our study identifies the STING-lipotoxicity axis as a key driver of viral hepatotoxicity, highlighting its potential as a therapeutic target for liver injury.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1804426

Authors: Yize Zhang, Yifei Li, Yingqiao Qin, Shaomei Liang, Kunpeng Liu, Xue Liang

Institutions: First Affiliated Hospital of Zhengzhou University, Guangxi University, The People's Hospital of Guangxi Zhuang Autonomous Region

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801