This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fingerote, R. J. Articles by Levy, G. A. Search for Related Content PubMed PubMed Citation Articles by Fingerote, R. J. Articles by Levy, G. A.

 Previous Article  |  Next Article 

J. Virol., Jul 1996, 4275-4282, Vol 70, No. 7
Copyright © 1996, American Society for Microbiology

Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity

RJ Fingerote, M Abecassis, MJ Phillips, YS Rao, EH Cole, J Leibowitz and GA Levy
Department of Medicine, Toronto Hospital, University of Toronto, Ontario, Canada.

Activation of the immune coagulation system has been implicated in the pathogenesis of liver injury following infection of inbred mice with murine hepatitis virus strain 3 (MHV-3). Following MHV-3 infection, macrophages isolated from MHV-3-susceptible and -semisusceptible inbred strains of mice express increased procoagulant activity (PCA), whereas macrophages from resistant strains express no increase in PCA over basal levels. The PCA induced by MHV-3 is a prothrombinase, encoded by the gene Fgl-2, which encodes a fibrinogen-like protein (musfiblp). In this study, MHV-3-resistant A/J mice treated with methylprednisolone prior to infection with MHV-3 developed elevated levels of alanine aminotransferase in serum and died within 10 days of infection, with histological findings of fulminant hepatitis. In vitro, macrophages isolated from A/J mice and pretreated with methylprednisolone produced a marked increase in functional PCA following infection with MHV-3. The PCA was shown to be a prothrombinase by its ability to cleave 125I- prothrombin. Northern blot analysis of RNA transcripts from these macrophages demonstrated increased transcription of the Fgl-2 gene relative to that in macrophages which had not been pretreated with methylprednisolone prior to MHV-3 infection. Methylprednisolone pretreatment of MHV-3-infected macrophages stabilized the Fgl-2 mRNA. Thus, loss of resistance to MHV-3 secondary to methylprednisolone therapy is associated with increased transcription and stability of Fgl- 2 mRNA resulting in expression of the Fgl-2 gene product, musfiblp. These results provide further insight into mechanisms of PCA regulation in response to MHV-3 infection in inbred strains of mice.

This article has been cited by other articles:

• Danenberg, H. D., Golomb, G., Groothuis, A., Gao, J., Epstein, H., Swaminathan, R. V., Seifert, P., Edelman, E. R. (2003). Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits. Circulation 108: 2798-2804 [Abstract] [Full Text]  
• Ontiveros, E., Kim, T. S., Gallagher, T. M., Perlman, S. (2003). Enhanced Virulence Mediated by the Murine Coronavirus, Mouse Hepatitis Virus Strain JHM, Is Associated with a Glycine at Residue 310 of the Spike Glycoprotein. J. Virol. 77: 10260-10269 [Abstract] [Full Text]  
• Danenberg, H. D., Welt, F. G. P., Walker, M. III, Seifert, P., Toegel, G. S., Edelman, E. R. (2002). Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits. Circulation 105: 2917-2922 [Abstract] [Full Text]  
• Chan, C. W. Y., Chan, M. W. C., Liu, M., Fung, L., Cole, E. H., Leibowitz, J. L., Marsden, P. A., Clark, D. A., Levy, G. A. (2002). Kinetic Analysis of a Unique Direct Prothrombinase, fgl2, and Identification of a Serine Residue Critical for the Prothrombinase Activity. J. Immunol. 168: 5170-5177 [Abstract] [Full Text]