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Updated: Aug 15, 2026
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis
1Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan. h-irie@rb3.so-net.or.jp
Abstract:
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.
Insights
Impaired macrophage response in mice infected with herpes simplex virus type 1 (HSV-1) led to acute yellow liver atrophy. This suggests inadequate immune cell function may underlie severe viral hepatitis, with liver damage potentially being apoptosis rather than necrosis.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Fulminant hepatitis can result from herpes simplex virus (HSV) or hepatitis virus infections.
- The specific host conditions predisposing to severe viral hepatitis remain debated.
Purpose of the Study:
- To investigate the role of impaired host defenses, specifically macrophage function, in the development of fulminant hepatitis.
- To elucidate the mechanism of hepatic damage in severe viral hepatitis.
Main Methods:
- Macrophage depletion in mice using silica administration.
- Subsequent intravenous injection with herpes simplex virus type 1 (HSV-1).
- Histopathological examination of liver tissues and assessment of viral replication and apoptosis.
Main Results:
- Mice with depleted macrophages exhibited rapid mortality and characteristic signs of acute yellow atrophy (shrunken, yellowish, hemorrhagic livers).
- Liver lesions showed confluent foci of apoptotic cells, extensive HSV replication, and DNA fragmentation indicative of apoptosis.
- The observed hepatic damage pattern mimicked massive hepatic necrosis but was characterized by apoptosis.
Conclusions:
- Inadequate macrophage response is a potential underlying condition for fulminant viral hepatitis.
- Massive hepatic damage in this context may represent virus-induced apoptosis of liver cells, not solely necrosis.
- This study highlights the critical role of immune surveillance in preventing severe outcomes of viral hepatitis.
