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Updated: Jan 12, 2026
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
Acute hepatic failure in IFN-gamma-deficient BALB/c mice after murine coronavirus infection
Shigeru Kyuwa1, Shinwa Shibata, Yoh-ichi Tagawa
1Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. akyuwa@mail.ecc.u-tokyo.ac.jp
Abstract:
We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) persists in interferon-gamma (IFN-gamma)-deficient C57BL/6 (B6-GKO) mice and results in subacute fatal peritonitis, which bears a resemblance to feline infectious peritonitis. To examine the role of other host factors in MHV infection in mice, IFN-gamma-deficient mice with a BALB/c background (BALB-GKO) were infected intraperitoneally with MHV and compared with B6-GKO mice. In contrast to B6-GKO mice, BALB-GKO mice died within 1 week due to acute hepatic failure. The viral titer of the liver in BALB-GKO mice was significantly higher than that in B6-GKO mice. All hepatocytes in BALB-GKO mice were necrotic at 5 days post-infection, which was clearly distinct from large but limited lesion in the liver from infected B6-GKO mice. The serum alanine aminotransferase activity of infected BALB-GKO mice were higher than that of B6-GKO mice and was paralleled with the severity of the pathological changes and viral titers in infected mice. Administration of exogenous IFN-gamma to BALB-GKO partially inhibited the acute death. These results indicate that BALB-GKO and B6-GKO mice clearly show different diseases following MHV infection, although wild type counterparts of both mice apparently showed the same clinical course after MHV infection.
Insights
Mouse hepatitis virus (MHV) infection causes different outcomes in interferon-gamma (IFN-gamma)-deficient mice. BALB/c background mice experienced acute liver failure, unlike C57BL/6 mice.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Mouse hepatitis virus (MHV) infection can persist in interferon-gamma (IFN-gamma)-deficient C57BL/6 mice, leading to fatal peritonitis.
- This condition resembles feline infectious peritonitis, suggesting potential parallels in disease mechanisms.
Purpose of the Study:
- To investigate the role of host genetic background in MHV infection severity.
- To compare the disease progression of MHV in IFN-gamma-deficient mice with different genetic backgrounds (BALB/c vs. C57BL/6).
Main Methods:
- Intraperitoneal infection of IFN-gamma-deficient mice on BALB/c (BALB-GKO) and C57BL/6 (B6-GKO) backgrounds with MHV.
- Comparison of clinical signs, mortality, viral titers, liver pathology, and serum alanine aminotransferase (ALT) levels between the two mouse groups.
- Administration of exogenous IFN-gamma to BALB-GKO mice to assess its therapeutic effect.
Main Results:
- BALB-GKO mice succumbed to acute hepatic failure within one week, exhibiting significantly higher liver viral titers and widespread hepatocyte necrosis.
- B6-GKO mice developed subacute peritonitis with limited liver lesions, as previously observed.
- Elevated serum ALT levels in BALB-GKO mice correlated with disease severity and viral load.
- Exogenous IFN-gamma administration partially protected BALB-GKO mice from acute death.
Conclusions:
- The genetic background of IFN-gamma-deficient mice significantly influences the outcome of MHV infection, leading to distinct disease phenotypes (acute liver failure vs. peritonitis).
- These findings highlight the critical role of IFN-gamma and potentially other host factors in controlling MHV pathogenesis.
- The differential susceptibility provides a valuable model for studying viral hepatitis and the immune response to MHV.
