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Journal of Virology, December 2002, p. 12823-12833, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12823-12833.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Theiler's Virus Infection of Primary Cultures of Bone Marrow-Derived Monocytes/Macrophages

Cécile Martinat,{dagger} Ignacio Mena, and Michel Brahic*

Unité des Virus Lents, CNRS URA 1930, Département de Virologie, Institut Pasteur, 75724 Paris Cedex 15, France

Received 5 April 2002/ Accepted 18 September 2002

Theiler's virus, a murine picornavirus, causes a persistent infection of macrophage/microglial cells in the central nervous systems of SJL/J mice. Viral replication is restricted in the majority of infected cells, whereas a minority of them contain large amounts of viral RNA and antigens. For the present work, we infected primary cultures of bone marrow monocytes/macrophages from SJL/J mice with Theiler's virus. During the first 10 h postinfection (p.i.), infected monocytes/macrophages were round and covered with filopodia and contained large amounts of viral antigens throughout their cytoplasm. Later on, they were large, flat, and devoid of filopodia and they contained only small amounts of viral antigens distributed in discrete inclusions. These two types of infected cells were very reminiscent of the two types of infected macrophages found in the spinal cords of SJL/J mice. At the peak of virus production, the viral yield per cell was approximately 200 times lower than that for BHK-21 cells. Cell death occurred in the culture during the first 24 h p.i. but not thereafter. No infected cells could be detected after 4 days p.i., and the infection never spread to 100% of the cells. This restriction was unchanged by treating the medium at pH 2 but was abolished by treating it with a neutralizing alpha/beta interferon antiserum, indicating a role for this cytokine in limiting virus expression in monocyte/macrophage cultures. The role of alpha/beta interferon was confirmed by the observation that monocytes/macrophages from IFNA/BR-/- mice were fully permissive.

* Corresponding author. Mailing address: Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 28, rue du Docteur Roux, 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: Taub Institute for the Aging Brain, Departments of Pathology and Neurology, Center for Neurobiology and Behavior, Columbia University, New York, NY 10032

Journal of Virology, December 2002, p. 12823-12833, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12823-12833.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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