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

Koji Hashimoto, Hiroko Minagawa, Yusuke Yanagi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)773-778
Number of pages6
JournalJournal of Hepatology
Volume39
Issue number5
DOIs
Publication statusPublished - Nov 2003

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Acute Liver Failure
Simplexvirus
Caspases
Apoptosis
Fas Ligand Protein
Liver
Wounds and Injuries
DNA Fragmentation
Virus Diseases
Caspase 3
Antigens
DNA Nucleotidylexotransferase
Viral DNA
Transferases
Reverse Transcriptase Polymerase Chain Reaction
Hepatitis
Cell Death
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Caspase-dependent apoptosis in fulminant hepatic failure induced by herpes simplex virus in mice. / Hashimoto, Koji; Minagawa, Hiroko; Yanagi, Yusuke.

In: Journal of Hepatology, Vol. 39, No. 5, 11.2003, p. 773-778.

Research output: Contribution to journalArticle

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