Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice

In the present study, a genetically restricted pathogenic agent, MHV-3, stimulates the PCA response of cells only from strains of mice susceptible to the pathologic effects of the virus. This, to our knowledge, is the first example of a normal genetic restriction of the PCA response and is characterized by maximum output of PCA by BALB/c mice that are fully susceptible to MHV-3, with a fatal outcome within 6-7 d, a moderate PCA response of C3H/St mice who develop enzymatic and histologic lesions of hepatitis (G. A. Levy, J. L. Leibowitz, and T. S. Edgington, manuscript in preparation), and no PCA response of mice fully resistant to MHV-3, as exemplified by the A/J strain. We have shown that these strains are all functionally capable of producing a PCA response to LPS 2 and also to antigen:antibody complexes (unpublished data) and that the magnitude of the PCA response is equivalent, a Therefore, the lack of response by the A/J strain to MHV-3 is specific for the stimulus. The response of cells from C3H/St mice is comparable to that observed for other unrestricted stimuli, such as LPS 2 or antigen:antibody complexes (15) and before this study would have been considered a maximum response. Of great interest is the unprecedented response of cells from BALB/c mice. It represents -30 times the response observed for any other previously examined stimulus, including those reported by other investigators (17) (18) (19) (20) . Whether or not the increased magnitude of the response represents increased synthesis of procoagulant molecules, a new and as yet uncharacterized initiator of the coagulation pathways or conformation realignment of either tissue factor or the monocyte prothrombinase (39) and amplification of activity by a cofactor such as factor Va (40) remains to be investigated.