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

R. J. Fingerote, M. Abecassis, M. J. Phillips, Y. S. Rao, E. H. Cole, J. Leibowitz, G. A. Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4275-4282
Number of pages8
JournalJournal of virology
Volume70
Issue number7
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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