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J Virol, May 1998, p. 4515-4519, Vol. 72, No. 5
Unité des Virus Lents, ERS 572 CNRS,
Institut Pasteur, 75724 Paris Cedex 15, France,1
and
University Hospital Zurich, Institute of Experimental
Immunology, 8091 Zürich, Switzerland2
Received 18 December 1997/Accepted 9 February 1998
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.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Theiler's Virus Infection of
Perforin-Deficient Mice


and
*
Corresponding author. Mailing address: Unité des
Virus Lents, ERS 572 CNRS, Institut Pasteur, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 87 70. Fax: 33 1 40 61 31 67. E-mail:
mbrahic{at}pasteur.fr.
Present address: Department of Microbiology and Immunology,
University of California
San Francisco, San Francisco, CA 94143.
Present address: Amgen Institute, Toronto, Ontario M5G 2M9,
Canada.
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