Caspase-dependent apoptosis in fulminant hepatic failure induced by herpes simplex virus in mice

Koji Hashimoto, Hiroko Minagawa, Yusuke Yanagi

研究成果: ジャーナルへの寄稿学術誌査読

11 被引用数 (Scopus)


Background/Aims: Herpes simplex virus (HSV) is known to induce fulminant hepatic failure. The aim of this study is to clarify the molecular basis of liver injury in HSV-induced hepatitis. Methods: Immunocompetent mice were inoculated with HSV or ultraviolet-inactivated HSV (UV-HSV) intravenously. Extent of liver injury was evaluated by changes of serum enzymes and histopathology. Apoptosis was assessed by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Immunohistochemistry for caspase-3 and Fas ligand was performed. Reverse transcriptase-polymerase chain reaction for Fas ligand was also performed. Results: All mice died of rapid and massive liver cell death after HSV infection, whereas no change was observed in mice after UV-HSV inoculation. The extent of viral replication and DNA fragmentation correlated well with the severity of liver injury. Caspase-3 was activated in the liver after HSV infection, but not UV-HSV. Positive reaction for TUNEL was observed not only in HSV-antigen positive cells but also in HSV-antigen negative cells. Fas ligand was induced in the liver infected with HSV, but not with UV-HSV. Conclusions: Caspase-dependent apoptosis is involved in HSV-associated liver injury. Not only viral replication but also non-viral factor such as Fas ligand may facilitate rapid development of this disease.

ジャーナルJournal of Hepatology
出版ステータス出版済み - 11月 2003

!!!All Science Journal Classification (ASJC) codes

  • 肝臓学


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