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Journal of Virology, June 2000, p. 5470-5476, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

H-2Dbminus /minus Mice Are Susceptible to Persistent Infection by Theiler's Virus

Arièle Azoulay-Cayla,1,dagger Sven Dethlefs,1,Dagger Béatrice Pérarnau,2,|| Eva-Lotta Larsson-Sciard,1,§ François A. Lemonnier,2 Michel Brahic,1,* and Jean-François Bureau1

Unité des Virus Lents, CNRS URA 1930,1 and Unité d'Immunité Cellulaire Antivirale,2 Institut Pasteur, 75724 Paris Cedex 15, France

Received 8 November 1999/Accepted 20 March 2000

H-2b mice are resistant to persistent infection of the central nervous system by Theiler's virus. They clear the infection 7 to 10 days after intracranial inoculation. Resistance maps to the H-2D gene and not to the H-2K gene and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) response. We used H-2b mice in which the H-2D or the H-2K gene had been inactivated to dissect the respective roles of these genes in resistance. We report that H-2D-/- but not H-2K-/- mice were susceptible to persistent infection. Furthermore, whereas H-2K-/- mice mounted a vigorous virus-specific CTL response, similar to that of control C57BL/6 mice, the CTL response of H-2D-/- mice was nil or minimal. Using target cells transfected with the H-2Db or the H-2Kb gene, we showed that the H-2K-restricted CTL response against the virus was minimal in H-2D-/- mice. These results demonstrate that the H-2Db and H-2Kb genes play nonredundant roles in the resistance to this persistent infection.


* Corresponding author. Mailing address: Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 28, rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33(0)1 45 68 87 70. Fax: 33(0)1 40 61 31 67. E-mail: mbrahic{at}pasteur.fr.

dagger Present address: Fédération de Neurologie, Hôpital de la Pitié-Salpêtrière, 75651 Paris Cedex 13, France.

Dagger Present address: McKinsey & Company, Inc., 80538 Munich, Germany.

§ Present address: Department of Immunology, Division of Investigative Science, ICSM Chelsea & Westminster Hospital, London SW10 9NH, United Kingdom.

|| Present address: Centre d'Immunologie de Marseille-Luminy, 13288 Marseille Cedex 9, France.


Journal of Virology, June 2000, p. 5470-5476, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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