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Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient in gamma interferon
1Department of Animal Pathology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan. kyuwa@gpo.kumamoto-u.ac.jp
Abstract:
Gamma interferon-deficient (IFN-gamma-/-) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-gamma-+/- and IFN-gamma+/+ mice, JHMV persisted in IFN-gamma-/- mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-gamma-/- mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-gamma protracted the survival time of IFN-gamma-/- mice after JHMV infection. These results demonstrate that IFN-gamma plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-gamma-/- mice, which bears a resemblance to feline infectious peritonitis in cats.
Insights
Gamma interferon (IFN-γ) is crucial for clearing mouse hepatitis virus (JHMV). Lacking IFN-γ leads to persistent JHMV infection and fatal peritonitis, a condition resembling feline infectious peritonitis.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Mouse hepatitis virus (JHMV) infection models are used to study viral pathogenesis.
- Gamma interferon (IFN-γ) is a key cytokine in the immune response to viral infections.
Purpose of the Study:
- To investigate the role of IFN-γ in JHMV infection and pathogenesis.
- To characterize the disease course in mice lacking IFN-γ during JHMV infection.
Main Methods:
- Infection of gamma interferon-deficient (IFN-γ-/-) mice and control mice (IFN-γ+/- and IFN-γ+/+) with JHMV.
- Observation of clinical signs, survival rates, and pathological changes.
- Administration of recombinant IFN-γ to JHMV-infected IFN-γ-/- mice.
Main Results:
- JHMV persisted in IFN-γ-/- mice, leading to death during the subacute phase, unlike in control mice.
- IFN-γ-/- mice developed severe peritonitis with fluid accumulation, but without significant hepatocyte damage.
- Recombinant IFN-γ administration prolonged survival in JHMV-infected IFN-γ-/- mice.
Conclusions:
- IFN-γ is essential for effective viral clearance of JHMV.
- Persistent JHMV infection in the absence of IFN-γ induces a distinct disease resembling feline infectious peritonitis.