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

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).

Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.

Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2).

Induction of macrophage procoagulant activity by murine hepatitis virus strain 3: role of tyrosine phosphorylation.

The induction of a unique macrophage procoagulant molecule by murine hepatitis virus strain 3 correlates with the severity of viral hepatitis. The role of tyrosine phosphorylation in the signalling pathway leading to procoagulant expression was studied. Murine hepatitis virus strain 3 initiated a rapid increase in phosphotyrosine accumulation.

A 2',5'-oligoadenylate analogue inhibits murine hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice.

Exposure of inbred mice to murine hepatitis virus strain 3 (MHV-3) causes a strain dependent spectrum of disease symptoms which correlates with induction of procoagulant activity (PCA) by macrophages. Previous studies have demonstrated a role for interferons in resistance to MHV-3 infection. These cytokines have both antiviral and immunoregulatory effects which may be crucial for MHV-3 resistance.