title: Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgl2 prothrombinase.
abstract: Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure.
authors.affiliation: Multi-Organ Transplant Program and Department of Medicine, Toronto Hospital, Ontario, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Ding
authors.forename: Q
authors.initials: Q
authors.lastname: Ning
authors.forename: M F
authors.initials: MF
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Leibowitz
authors.forename: K M
authors.initials: KM
authors.lastname: Peltekian
authors.forename: E H
authors.initials: EH
authors.lastname: Cole
authors.forename: L S
authors.initials: LS
authors.lastname: Fung
authors.forename: C
authors.initials: C
authors.lastname: Holloway
authors.forename: P A
authors.initials: PA
authors.lastname: Marsden
authors.forename: H
authors.initials: H
authors.lastname: Yeger
authors.forename: M J
authors.initials: MJ
authors.lastname: Phillips
authors.forename: G A
authors.initials: GA
authors.lastname: Levy
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D005340:Fibrinogen; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus; D012333:RNA, Messenger; D011817:Rabbits; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C490637:Fgl2 protein, mouse; D012333:RNA, Messenger; D005340:Fibrinogen; D013925:Thromboplastin