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HSV hepatitis in the mouse: a light and electron microscopic study with immunohistology and in situ hybridization
P Schirmacher1, M Wörsdörfer, K Lübbe
1Pathologisches Institut, Johannes Gutenberg-Universität, Mainz, Federal Republic of Germany.
Abstract:
In order to characterize better the morphology and immune response in acute necrotizing HSV infection, murine HSV hepatitis was examined. BALB/c mice were inoculated intraperitoneally with 10(6) plaque-forming units (PFU) of HSV-1 (Lenette) and HSV-2 (D316). In both groups half the animals were pretreated with silica particles to block macrophage function. Up to 6 days after infection four mice from each group were sacrificed at daily intervals and the livers were examined by light and electron microscopy, immunohistology, in situ hybridization, combined immunohistology/in situ hybridization and titration of viral PFU. HSV-2 infected mice developed severe necrotizing hepatitis with persistence of HSV in the liver tissue until the end of the study. HSV-1 infected mice rapidly eliminated the virus and revealed only small necrotic foci. Early phase alterations and necrotic phase lesions were distinguished and characterized and morphologic evidence of a direct cytopathic effect of HSV was detected. A specific immune reaction in late stages appeared to be mediated by T4-positive T-lymphocytes. In situ hybridization and immunohistochemistry showed a close correlation with virus titration and were valuable in characterizing early phases and in the assessment of prognosis and differential diagnosis.
Insights
Herpes Simplex Virus type 2 (HSV-2) causes severe necrotizing hepatitis in mice, while HSV-1 is cleared rapidly. Immune responses, particularly T4-lymphocytes, play a role in controlling HSV infection.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Herpes Simplex Virus (HSV) infections can lead to hepatitis, but the specific host responses and morphological changes differ between HSV types.
- Understanding the pathogenesis of HSV hepatitis is crucial for diagnosis and treatment.
Purpose of the Study:
- To characterize the morphology and immune response in murine models of acute necrotizing HSV hepatitis.
- To compare the effects of HSV-1 and HSV-2 infection on the liver.
Main Methods:
- BALB/c mice were infected with HSV-1 or HSV-2 and macrophage function was modulated with silica.
- Liver tissues were analyzed using light and electron microscopy, immunohistology, in situ hybridization, and viral plaque-forming unit (PFU) titration.
- Mice were monitored for up to 6 days post-infection.
Main Results:
- HSV-2 infection resulted in severe necrotizing hepatitis with persistent virus, while HSV-1 infection led to rapid viral clearance and minimal necrosis.
- Direct cytopathic effects of HSV were observed, and distinct early and necrotic phase lesions were characterized.
- T4-positive T-lymphocytes were identified as mediators of the immune response in later stages of infection.
Conclusions:
- HSV-2 induces a more severe necrotizing hepatitis than HSV-1 in mice.
- In situ hybridization and immunohistochemistry are valuable tools for assessing HSV hepatitis prognosis and diagnosis.
- The study highlights the differential roles of HSV types in hepatitis pathogenesis and the involvement of specific immune cells.