{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:37:06Z","timestamp":1777361826257,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371774"],"award-info":[{"award-number":["82371774"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500745"],"award-info":[{"award-number":["82500745"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u20132010) to analyze correlations between hepatic steatosis and injury biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1804426","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:42:26Z","timestamp":1777358546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of STING alleviates lipotoxicity in viral-infected primary mouse hepatocytes and viral hepatitis-associated liver damage"],"prefix":"10.3389","volume":"17","author":[{"given":"Yize","family":"Zhang","sequence":"first","affiliation":[{"name":"Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingqiao","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaomei","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunpeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangxi Academy of Medical Sciences, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1053\/jhep.2001.24432","article-title":"Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity","volume":"33","author":"Adinolfi","year":"2001","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1136\/gut.2005.069757","article-title":"Steatosis in chronic hepatitis C: why does it really matter?","volume":"55","author":"Asselah","year":"2006","journal-title":"Gut"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1073\/pnas.94.4.1200","article-title":"Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets","volume":"94","author":"Barba","year":"1997","journal-title":"Proc. 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