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Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis
M T Lin1, S A Stohlman, D R Hinton
1Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Abstract:
Perforin-deficient [perforin (-/-)] mice were infected with two strains of JHM virus (JHMV) to analyze the role of perforin-mediated cytotoxicity in acute lethal and subacute central nervous system (CNS) infections. During both acute and subacute infections, the overall mortality of the perforin (-/-) mice was not different from that of the controls. Perforin (-/-) mice survived longer than the controls, consistent with reduced morbidity. Both strains of virus were cleared from the perforin (-/-) mice as in the controls; however, the rate of clearance was delayed in the perforin (-/-) mice, indicating that perforin-mediated cytolysis is involved in viral clearance. The absence of perforin-mediated cytolysis did not prevent encephalomyelitis or extensive demyelination. Cells undergoing apoptosis were detected in the CNS of both the perforin (-/-) and control groups, indicating that perforin is not essential for programmed cell death. Neutralizing antibodies were not detected in either group of mice until day 9 postinfection, when the majority of the virus had been cleared. These data further confirm the importance of cell-mediated cytotoxicity and suggest that additional components of the immune response contribute to the clearance of JHMV from the CNS.
Insights
Perforin-deficient mice showed delayed viral clearance but no increased mortality from JHMV infection. This highlights cell-mediated cytotoxicity
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Perforin-mediated cytotoxicity is crucial for immune responses against viral infections.
- The role of perforin in central nervous system (CNS) viral infections, such as those caused by the JHM virus (JHMV), requires further elucidation.
Purpose of the Study:
- To investigate the role of perforin-mediated cytotoxicity in JHMV-induced acute lethal and subacute CNS infections.
- To determine if perforin deficiency impacts JHMV clearance, morbidity, mortality, and the development of neuropathology.
Main Methods:
- Infection of perforin-deficient (perforin -/-) mice and control mice with two strains of JHMV.
- Monitoring of mortality, morbidity, viral clearance, and neuropathological changes (encephalomyelitis, demyelination).
- Detection of apoptotic cells and neutralizing antibodies in the CNS.
Main Results:
- Perforin deficiency did not alter overall mortality but led to delayed viral clearance from the CNS.
- Perforin (-/-) mice exhibited reduced morbidity and survived longer.
- Encephalomyelitis and demyelination occurred in both groups, and perforin was not essential for apoptosis.
Conclusions:
- Perforin-mediated cytolysis plays a role in the rate of JHMV clearance from the CNS.
- Cell-mediated cytotoxicity is important, but other immune components also contribute to JHMV clearance.
- Perforin is not essential for JHMV-induced apoptosis or neuropathology in this model.