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 novel fgl2 prothrombinase gene and elevated procoagulant activity in those strains that produce fulminant hepatitis. Chinese hamster ovary cells cotransfected with a construct expressing nucleocapsid protein from susceptible strains and with a luciferase reporter construct containing the fgl2 promoter showed a 6-fold increase in luciferase activity compared with nontransfected cells or cells cotransfected with a construct expressing nucleocapsid protein from resistant strains. Two deletions found at coding sites 111-123 and 1143-1145 of structural domains I and III, respectively, of the nucleocapsid gene may account for the differences between pathogenic and nonpathogenic strains. Preliminary mapping of the fgl2 promoter has defined a region from -372 to -306 upstream from the ATG translation initiation site to be responsive 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 transcription of the fgl2 prothrombinase gene. These studies provide new insights into the role of the nucleocapsid gene in the pathogenesis of viral hepatitis.
Ning
Q
Q
Multi-Organ Transplant Program and Departments of Medicine and Pathology, Toronto Hospital, St. Michael's Hospital, and the University of Toronto, Toronto, Ontario M5G 2C4, Canada.
Liu
M
M
Kongkham
P
P
Lai
M M
MM
Marsden
P A
PA
Tseng
J
J
Pereira
B
B
Belyavskyi
M
M
Leibowitz
J
J
Phillips
M J
MJ
Levy
G
G
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus; D019251:Nucleocapsid / Q000494:pharmacology*; D019590:Nucleocapsid Proteins; D011401:Promoter Regions, Genetic; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
C490637:Fgl2 protein, mouse; D019590:Nucleocapsid Proteins; C099600:nucleocapsid protein, Hepatitis virus; D005340:Fibrinogen; D013925:Thromboplastin