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Hepatic pathology resulting from mouse hepatitis virus S infection in severe combined immunodeficiency mice
D S Huang1, S N Emancipator, D R Fletcher
1Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106-4389, USA.
Abstract:
Mouse hepatitis virus (MHV) is a pervasive pathogen that causes morbidity and mortality in mouse colonies worldwide. Although it is not a major cause of mortality in immunocompetent mice, infections from MHV strains of lower virulence can be fatal to athymic nude mice. The histopathologic features and alterations of serum biochemical parameters resulting from infection with a low-virulence MHV strain in severe combined immunodeficiency (scid) mice has not been well described. Thus we recently studied the disease caused by MHV-S in scid mice after intranasal inoculation. Mouse hepatitis virus infection in scid mice, which have severe defects of B and T cells, may be highly lethal, resulting in immediate mortality. However, our results indicate that scid mice survived for an average of 12 to 14 days after infection with doses of MHV up to 10(7) PFU/mouse. The virus caused a significant increase in serum enzyme activities and bilirubin concentration associated with histologically demonstrable hepatocellular injury at postinoculation days 3, 4, and 8. Furthermore, virus was detected in mouse liver homogenates and nasal and bronchial lavage specimens. These results provide valuable information regarding the histopathologic and biochemical consequences of MHV-S infection in scid mice.
Insights
Mouse hepatitis virus (MHV) infection in severe combined immunodeficiency (scid) mice causes liver damage and elevated bilirubin, though scid mice survived longer than expected. This study details the histopathologic and biochemical effects of MHV-S in scid mice.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Mouse hepatitis virus (MHV) is a common pathogen in mouse colonies.
- While typically not fatal in immunocompetent mice, MHV can be lethal to immunodeficient strains like athymic nude mice.
- The effects of low-virulence MHV strains on severe combined immunodeficiency (scid) mice are not well-documented.
Purpose of the Study:
- To investigate the histopathologic and serum biochemical changes in scid mice infected with a low-virulence MHV strain (MHV-S).
- To characterize the disease progression and outcomes of MHV-S infection in scid mice.
Main Methods:
- Severe combined immunodeficiency (scid) mice were intranasally inoculated with MHV-S.
- Mice were monitored for survival, and serum biochemical parameters were analyzed.
- Histopathologic examination of tissues was performed.
- Virus presence was confirmed in liver homogenates and lavage specimens.
Main Results:
- Scid mice survived an average of 12–14 days post-infection, even at high viral doses (up to 10^7 PFU/mouse).
- Significant increases in serum enzyme activities and bilirubin concentration were observed.
- Histologically confirmed hepatocellular injury was evident at 3, 4, and 8 days post-inoculation.
- MHV was detected in liver, nasal, and bronchial samples.
Conclusions:
- MHV-S infection in scid mice leads to significant liver injury and biochemical alterations.
- Despite immune deficiencies, scid mice exhibited a measurable survival period after MHV-S infection.
- The findings provide crucial data on the consequences of MHV-S in scid mouse models.