Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis.
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.
Lin
M T
MT
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Stohlman
S A
SA
Hinton
D R
DR
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D004679:Encephalomyelitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D017353:Gene Deletion; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin