Related Experiment Videos
Genetic resistance to mouse hepatitis virus correlates with absence of virus-binding activity on target tissues
Abstract:
The molecular mechanism of genetic resistance of inbred mouse strains to mouse hepatitis virus, a murine coronavirus, was studied by comparing virus binding to plasma membranes of intestinal epithelium or liver from susceptible BALB/c and resistant SJL/J mice with a new solid-phase assay for virus-binding activity. Virus bound to isolated membranes from susceptible mice, but not to membranes from resistant mice. F1 progeny of SJL/J X BALB/c mice had an intermediate level of virus-binding activity on their enterocyte and hepatocyte membranes. This correlated well with previous studies showing that susceptibility to mouse hepatitis virus strain A59 is controlled by a single autosomal dominant gene (M. S. Smith, R. E. Click, and P. G. W. Plagemann, J. Immunol. 133:428-432). Because virus binding was not prevented by treating membranes with sodium dodecyl sulfate, the virus-binding molecule could be identified by a virus overlay protein blot assay. Virus bound to a single broad band of Mr 100,000 to 110,000 in membranes from hepatocytes or enterocytes of susceptible BALB/c and semisusceptible C3H mice, but no virus-binding band was detected in comparable preparations of resistant SJL/J mouse membranes. Therefore, SJL/J mice may be resistant to mouse hepatitis virus A59 infection because they lack a specific virus receptor which is present on the plasma membranes of target cells from genetically susceptible BALB/c and semisusceptible C3H mice.
Insights
Genetic resistance in mice to mouse hepatitis virus (MHV) is linked to the absence of a specific viral receptor on cell membranes. This finding explains why certain mouse strains are naturally resistant to MHV infection.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Mouse hepatitis virus (MHV) is a significant pathogen in mice.
- Genetic factors influence susceptibility and resistance to MHV infection among inbred mouse strains.
Purpose of the Study:
- To elucidate the molecular mechanism underlying genetic resistance to MHV in mice.
- To identify the specific viral or host factors involved in MHV susceptibility.
Main Methods:
- A novel solid-phase assay was developed to measure virus-binding activity to plasma membranes.
- Virus overlay protein blot assay was employed to identify the virus-binding molecule.
- Comparison of virus binding to intestinal and liver cell membranes from susceptible (BALB/c) and resistant (SJL/J) mice.
Main Results:
- Virus binding was observed in membranes from susceptible mice but not in resistant mice.
- F1 progeny exhibited intermediate virus-binding activity, suggesting a single gene control.
- A specific protein band (Mr 100,000-110,000) was identified as the virus-binding molecule in susceptible mice, absent in resistant mice.
Conclusions:
- Resistance to MHV strain A59 in SJL/J mice is likely due to the absence of a specific viral receptor on target cell plasma membranes.
- The identified virus-binding molecule is crucial for MHV entry and infection.
- This research provides a molecular basis for understanding genetic resistance to coronavirus infections.