PMID- 14568260
OWN - NLM
STAT- MEDLINE
DCOM- 20040720
LR  - 20190817
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 39
IP  - 5
DP  - 2003 Nov
TI  - Caspase-dependent apoptosis in fulminant hepatic failure induced by herpes 
      simplex virus in mice.
PG  - 773-8
AB  - 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.
FAU - Hashimoto, Koji
AU  - Hashimoto K
AD  - Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, 
      Japan.
FAU - Minagawa, Hiroko
AU  - Minagawa H
FAU - Yanagi, Yusuke
AU  - Yanagi Y
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - DNA Fragmentation
MH  - Disease Progression
MH  - Fas Ligand Protein
MH  - Herpes Simplex/*complications
MH  - Immunohistochemistry
MH  - Liver Failure/metabolism/pathology/*physiopathology/*virology
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Time Factors
MH  - Virus Replication
EDAT- 2003/10/22 05:00
MHDA- 2004/07/21 05:00
CRDT- 2003/10/22 05:00
PHST- 2003/10/22 05:00 [pubmed]
PHST- 2004/07/21 05:00 [medline]
PHST- 2003/10/22 05:00 [entrez]
AID - S0168827803003854 [pii]
AID - 10.1016/s0168-8278(03)00385-4 [doi]
PST - ppublish
SO  - J Hepatol. 2003 Nov;39(5):773-8. doi: 10.1016/s0168-8278(03)00385-4.