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Journal of Virology, July 2006, p. 6834-6843, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00432-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Both Spike and Background Genes Contribute to Murine Coronavirus Neurovirulence

Kathryn T. Iacono,{dagger} Lubna Kazi,{ddagger} and Susan R. Weiss*

Department of Microbiology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania

Received 1 March 2006/ Accepted 24 April 2006

Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic phenotypes. Infection with the A59 strain of MHV induces both encephalitis and hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis with little, if any, hepatitis. The pathogenic phenotype for each strain is determined by the genetic composition of the viral genome, as well as the host immune response. Using isogenic recombinant viruses with A59 background genes differing only in the spike gene, we have previously shown that high neurovirulence is associated with the JHM spike protein, the protein responsible for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall, and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic recombinant viruses with JHM background genes expressing either the JHM or A59 spike, we have further investigated the roles of viral genes in pathogenesis. Here, we demonstrate that the high neurovirulence of JHM is associated with accelerated spread through the brain and a heightened innate immune response that is characterized by high numbers of infiltrating neutrophils and macrophages, suggesting an immunopathogenic component to neurovirulence. While expression of the JHM spike is sufficient to confer a neurovirulent phenotype, as well as increased macrophage infiltration, background genes contribute to virulence as well, at least in part, by dictating the extent of the T-cell immune response.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania, School of Medicine, 36th Street and Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 898-8013. Fax: (215) 573-4858. E-mail: weisssr{at}mail.med.upenn.edu.

{dagger} Present address: Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA.

{ddagger} Present address: Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA.

Journal of Virology, July 2006, p. 6834-6843, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00432-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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