The nucleocapsid protein of murine hepatitis virus type 3 induces transcription of the novel fgl2 prothrombinase gene

Using a set of parental and recombinant murine hepatitis virus strains, we demonstrate that the nucleocapsid protein induces transcription of the nove l fg12 prothrombinase gene and elevated procoagulant activity in those stra ins that produce fulminant hepatitis. Chinese hamster ovary cells cotransfe cted with a construct expressing nucleocapsid protein from susceptible stra ins and with a luciferase reporter construct containing the fg12 promoter s howed a B-fold increase in luciferase activity compared with nontransfected cells or cells cotransfected with a construct expressing nucleocapsid prot ein from resistant strains. Two deletions found at coding sites 111-123 and 1143-1145 of structural domains I and III, respectively, of the nucleocaps id gene may account for the differences between pathogenic and nonpathogeni c strains. Preliminary mapping of the fg12 promoter has defined a region fr om -372 to -306 upstream from the ATG translation initiation site to be res ponsive to nucleocapsid protein. Hence, mapping of genetic determinants in parental and recombinant strains demonstrates that the nucleocapsid protein of strains that induce fulminant hepatitis is responsible for transcriptio n of the fg12 prothrombinase gene. These studies provide new insights into the role of the nucleocapsid gene in the pathogenesis of viral hepatitis.