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J Virol, May 1998, p. 4515-4519, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Theiler's Virus Infection of Perforin-Deficient Mice

Claudia Pena Rossi,1,dagger Andrés McAllister,1,dagger Myriam Tanguy,1 David Kägi,2,Dagger and Michel Brahic1,*

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.

* 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.

dagger Present address: Department of Microbiology and Immunology, University of California---San Francisco, San Francisco, CA 94143.

Dagger Present address: Amgen Institute, Toronto, Ontario M5G 2M9, Canada.

J Virol, May 1998, p. 4515-4519, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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