title: Resistance of naive mice to murine hepatitis virus strain 3 requires development of a Th1, but not a Th2, response, whereas pre-existing antibody partially protects against primary infection.
abstract: Murine hepatitis virus strain 3 (MHV-3) produces a strain-dependent spectrum of disease. The development of liver necrosis has been shown to be related to production of a unique macrophage procoagulant activity (PCA), encoded by the gene fgl-2, in susceptible mice. These studies were designed to examine the influence of Th1/Th2 cells on resistance/susceptibility and production of macrophage PCA in resistant (A/J) and susceptible (BALB/cJ) strains of mice following infection with MHV-3. Immunization of A/J mice with MHV-3 induced a Th1 cellular immune response, and one Th1 cell line (3E9.1) protected susceptible mice and inhibited PCA production by macrophages both in vitro and in vivo. In contrast, immunization of BALB/cJ mice with an attenuated variant of MHV-3 derived from passaging MHV-3 in YAC-1 cells resulted in a Th2 response. Transfer of spleen cells and T cell lines from immunized BALB/cJ mice failed to protect naive susceptible syngeneic mice from infection with MHV-3 and augmented macrophage PCA production to MHV-3 in vitro. However, serum from immunized BALB/cJ mice contained high titrated neutralizing Ab that protected naive BALB/cJ animals from lethal primary MHV-3 infection. These results demonstrate that susceptible BALB/cJ mice generate a Th2 response following MHV-3 infection and that these Th2 cells neither inhibit MHV-3-induced macrophage PCA production nor protect naive mice from MHV-3 infection. The results suggest that Ab protects against primary infection but cannot eradicate ongoing infection. Thus, these data define the differential role of Th1/Th2 lymphocytes in primary and secondary MHV-3 infection and emphasize the importance of PCA in the pathogenesis of MHV-3 infection.
authors.affiliation: Department of Surgery, The Toronto Hospital-University of Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Pope
authors.forename: S W
authors.initials: SW
authors.lastname: Chung
authors.forename: T
authors.initials: T
authors.lastname: Mosmann
authors.forename: J L
authors.initials: JL
authors.lastname: Leibowitz
authors.forename: R M
authors.initials: RM
authors.lastname: Gorczynski
authors.forename: G A
authors.initials: GA
authors.lastname: Levy
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000276:immunology; D002460:Cell Line; D018352:Coronavirus Infections / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000517:prevention & control*; D007113:Immunity, Innate; D007116:Immunization, Passive; D016219:Immunotherapy, Adoptive; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology*; D013154:Spleen / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000821:virology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001779:Blood Coagulation Factors; D014765:Viral Vaccines; C045072:macrophage procoagulant activity