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Differences between BALB/c and C57BL/6 mice in mouse hepatitis virus replication in primary hepatocyte culture
Shigeru Kyuwa1, Seiji Kawamura, Yoh-ichi Tagawa
1Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
Abstract:
We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) resulted in acute hepatic failure accompanying extremely elevated viral growth in the liver in interferon-gamma-deficient BALB/c (BALB-GKO), but not C57BL/6 (B6-GKO) mice. To examine the basis of the strain difference against MHV infection in interferon-gamma-deficient mice, viral replication in primary hepatocyte cultures from BALB/c and B6 mice with or without the IFN-gamma gene was compared in vitro. The MHV replication in BALB/c hepatocytes with or without the IFN-gamma gene was significantly higher than that in B6 hepatocytes with or without the IFN-gamma gene, suggesting that there is a strain difference in MHV replication in hepatocytes. Since a significant difference in MHV replication in hepatocytes was not observed between wild type and IFN-gamma-deficient mice of the same genetic background, the phenomenon is thought to be independent of IFN-gamma. However, pretreatment of hepatocytes with recombinant mouse interferon-gamma inhibited MHV replication in a dose-dependent fashion. The results are discussed with respect to the pathology of MHV infection in mice with or without the IFN-gamma gene.
Insights
Mouse hepatitis virus (MHV) replicates more in BALB/c mouse liver cells than in B6 mouse cells, irrespective of interferon-gamma (IFN-γ) presence. IFN-γ treatment inhibits MHV replication in a dose-dependent manner.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Interferon-gamma (IFN-γ) deficiency leads to severe mouse hepatitis virus (MHV) infection in BALB/c mice, but not C57BL/6 mice.
- This suggests a strain-dependent difference in MHV pathogenesis related to IFN-γ.
- Investigating the basis of this strain difference in MHV infection is crucial.
Purpose of the Study:
- To compare in vitro MHV replication in primary hepatocytes from BALB/c and C57BL/6 mice.
- To determine the role of interferon-gamma (IFN-γ) in strain-specific MHV replication in hepatocytes.
- To elucidate the mechanisms underlying differential MHV susceptibility between mouse strains.
Main Methods:
- Primary hepatocyte cultures were established from BALB/c and C57BL/6 mice, with and without the interferon-gamma (IFN-γ) gene.
- Viral replication of mouse hepatitis virus (MHV) was quantified in these hepatocyte cultures.
- Hepatocytes were pretreated with recombinant mouse IFN-γ to assess its effect on MHV replication.
Main Results:
- MHV replication was significantly higher in BALB/c hepatocytes compared to C57BL/6 hepatocytes, regardless of IFN-γ gene status.
- No significant difference in MHV replication was observed between wild-type and IFN-γ-deficient hepatocytes of the same genetic background.
- Recombinant mouse IFN-γ inhibited MHV replication in hepatocytes in a dose-dependent manner.
Conclusions:
- A strain-specific difference in hepatocyte susceptibility to MHV replication exists between BALB/c and C57BL/6 mice.
- This difference appears independent of the presence or absence of the IFN-γ gene in the hepatocytes.
- Interferon-gamma (IFN-γ) plays a crucial role in controlling MHV replication within hepatocytes, independent of the mouse strain's genetic background.