Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis.
Infection with herpes simplex virus or hepatitis viruses can lead to fulminant hepatitis, but there is controversy about the underlying conditions needed for such disease. To investigate how the impairment of host defences might be involved, macrophages were depleted by administration of silica to mice before intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the liver lobules; these rapidly became confluent and zonal over time. The overall lesion pattern was similar to massive hepatic necrosis, and there was extensive HSV replication in the liver lesions. In the liver, DNA fragmentation characteristic of apoptosis followed the time course of HSV-1 propagation. These findings suggest that one of the underlying conditions for fulminant viral hepatitis may be inadequate macrophage response, and that the massive hepatic damage, often defined as cell necrosis, may actually be apoptosis of liver cells subsequent to virus infection.
Irie
H
H
Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan. h-irie@rb3.so-net.or.jp
Koyama
H
H
Kubo
H
H
Fukuda
A
A
Aita
K
K
Koike
T
T
Yoshimura
A
A
Yoshida
T
T
Shiga
J
J
Hill
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014779:Virus Replication
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase