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Journal of Virology, April 2004, p. 3398-3406, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3398-3406.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Coronavirus Neurovirulence Correlates with the Ability of the Virus To Induce Proinflammatory Cytokine Signals from Astrocytes and Microglia

Yun Li, Li Fu, Donna M. Gonzales, and Ehud Lavi*

Division of Neuropathology, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 20 August 2003/ Accepted 8 December 2003

The molecular and cellular basis of coronavirus neurovirulence is poorly understood. Since neurovirulence may be determined at the early stages of infection of the central nervous system (CNS), we hypothesize that it may depend on the ability of the virus to induce proinflammatory signals from brain cells for the recruitment of blood-derived inflammatory cells. To test this hypothesis, we studied the interaction between coronaviruses (mouse hepatitis virus) of different neurovirulences with primary cell cultures of brain immune cells (astrocytes and microglia) and mouse tissues. We found that the level of neurovirulence of the virus correlates with its differential ability to induce proinflammatory cytokines (interleukin 12 [IL-12] p40, tumor necrosis factor alpha, IL-6, IL-15, and IL-1ß) in astrocytes and microglia and in mouse brains and spinal cords. These findings suggest that coronavirus neurovirulence may depend on a novel discriminatory ability of astrocytes and microglia to induce a proinflammatory response in the CNS.

* Corresponding author. Mailing address: University of Pennsylvania, School of Medicine, Division of Neuropathology, Department of Pathology and Laboratory Medicine, 613 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, PA 19104-6100. Phone: (215) 898-8198. Fax: (215) 898-9969. E-mail: lavi{at}mail.med.upenn.edu.

Journal of Virology, April 2004, p. 3398-3406, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3398-3406.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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