FULMINANT HEPATIC-FAILURE IN MURINE HEPATITIS-VIRUS STRAIN-3 INFECTION - TISSUE-SPECIFIC EXPRESSION OF A NOVEL FGL2 PROTHROMBINASE

Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis vi rus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which enc odes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows fo r fundamental studies to determine the molecular basis for fulminant l iver failure. Transcription of the fgl2 gene and translation of the pr otein it encodes were examined in the liver and other organs of suscep tible mice following MHV-3 infection. No constitutive expression of th e fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in l arge amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amo unts in the kidney and brain. There was sequential detection of fgl2 p rothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was all owed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the s elective expression of this novel fgl2 prothrombinase in the pathogene sis of MHV-3-induced fulminant liver failure.