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Theiler's virus infection of perforin-deficient mice
C P Rossi1, A McAllister, M Tanguy
1Unité des Virus Lents, ERS 572 CNRS, Institut Pasteur, Paris, France.
Abstract:
Theiler's virus, a murine picornavirus, infects the central nervous systems of C57BL/6 mice and is cleared after approximately 10 days by a process which requires CD8+ cytotoxic T cells. We used perforin-deficient C57BL/6 mice to test the role of this protein in viral clearance. Perforin-deficient mice died from viral encephalomyelitis between days 12 and 18 postinoculation. They had high levels of viral RNA in their central nervous systems until the time of death. In contrast, viral RNA had disappeared by day 11 postinoculation in wild-type C57BL/6 mice. Cytotoxic T cells can kill infected cells by two main mechanisms: the secretion of the pore-forming protein perforin or the interaction of the Fas ligand with the apoptosis-inducing Fas molecule on the target cell. Our results demonstrate that clearance of Theiler's virus from the central nervous system in C57BL/6 mice is perforin dependent.
Insights
Theiler
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Theiler's virus (a murine picornavirus) infects the central nervous system (CNS) of C57BL/6 mice.
- Viral clearance from the CNS is mediated by CD8+ cytotoxic T cells.
- Cytotoxic T cells utilize perforin or Fas ligand pathways to eliminate infected cells.
Purpose of the Study:
- To investigate the role of perforin in Theiler's virus clearance from the CNS.
- To determine if perforin is essential for the cytotoxic T cell-mediated immune response against Theiler's virus.
Main Methods:
- Utilized perforin-deficient C57BL/6 mice and wild-type C57BL/6 mice.
- Inoculated mice with Theiler's virus and monitored for viral encephalomyelitis.
- Quantified viral RNA levels in the CNS over time postinoculation.
Main Results:
- Perforin-deficient mice succumbed to viral encephalomyelitis between days 12-18 postinoculation.
- High levels of viral RNA persisted in the CNS of perforin-deficient mice until death.
- Wild-type mice cleared viral RNA from the CNS by day 11 postinoculation.
Conclusions:
- The clearance of Theiler's virus from the CNS of C57BL/6 mice is dependent on perforin.
- Perforin plays a critical role in the cytotoxic T cell-mediated immune response against Theiler's virus infection in the CNS.