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Duration of mouse hepatitis virus infection: studies in immunocompetent and chemically immunosuppressed mice
1Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510.
Abstract:
The duration of mouse hepatitis virus (MHV) infection was examined in mice inoculated intranasally with selected strains of MHV. Following inoculation with virulent MHV-JHM, genetically susceptible BALB/c mice and resistant CD1 mice had detectable virus in the brain at 1 month, but not later intervals up to 12 months. BALB/c mice infected with avirulent MHV-S or MHV-1 had no detectable virus in brains at 1 month or thereafter. Immunosuppression of BALB/c mice with treatment regimens of hydrocortisone acetate or cyclophosphamide at 1 and 2 months after infection with MHV-JHM did not activate detectable virus in liver or increase the prevalence or degree of brain infection. Immunosuppression with these drugs during the acute phase of MHV-JHM infection influenced MHV infection, based on virus quantification in livers, but timing of drug treatment relative to MHV infection was critical. Mice infected with MHV developed IgG serum antibody titers that persisted without decline for up to 1 year after infection. Antibody titers varied with mouse genotype and infecting virus. These studies, using intranasal inoculation, support the conclusions of others, using other routes of inoculation, that MHV infection is not persistent in adult, immunocompetent mice.
Insights
Mouse hepatitis virus (MHV) infection is not persistent in adult mice. Studies show MHV is undetectable in brains after one month, even after immunosuppression, with lasting antibody titers observed.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Mouse hepatitis virus (MHV) is a significant pathogen in mouse models.
- Understanding the persistence of MHV infection is crucial for research and disease management.
Purpose of the Study:
- To investigate the duration and persistence of mouse hepatitis virus (MHV) infection in adult mice following intranasal inoculation.
- To determine the impact of immunosuppression on MHV persistence in different mouse strains.
Main Methods:
- Intranasal inoculation of BALB/c and CD1 mice with virulent (MHV-JHM) and avirulent (MHV-S, MHV-1) MHV strains.
- Detection of viral presence in brain and liver tissues at various time points up to 12 months post-infection.
- Administration of immunosuppressive agents (hydrocortisone acetate, cyclophosphamide) at different stages of infection.
Main Results:
- Detectable MHV in the brain was limited to 1 month post-infection with MHV-JHM in both susceptible and resistant mice.
- Avirulent MHV strains (MHV-S, MHV-1) did not result in detectable brain virus at any time point.
- Immunosuppression during the acute phase affected liver viral load, but not brain infection persistence; later immunosuppression had no effect.
- Persistent IgG serum antibody titers were observed for up to 1 year, varying by mouse genotype and virus strain.
Conclusions:
- Mouse hepatitis virus (MHV) infection is not persistent in adult, immunocompetent mice, regardless of genetic susceptibility or viral strain.
- The timing of immunosuppression is critical in influencing MHV infection dynamics, primarily during the acute phase.
- Persistent antibody responses indicate a resolved infection rather than chronic viral presence.