Acquired immunity of A/J mice to mouse hepatitis virus 3 infection: dependence on interferon-gamma synthesis and macrophage sensitivity to interferon-gamma.
Coronavirus-free A/J mice (A/J-), in contrast to those naturally infected with coronavirus (A/J+), were shown to be susceptible to experimental infection with our strain of mouse hepatitis virus 3 (MHV3). A/J- mice experimentally hyperimmunized with inactivated MHV3 (A/Ji) became resistant to challenge with this virus. BALB/c mice free of (BALB/c-) or naturally infected with (BALB/c+) coronavirus, or hyperimmunized with inactivated MHV3 (BALB/ci), were always fully susceptible. All susceptible mice developed an acute hepatitis with a high virus titre in the tissues. Resistance mice developed a mild disease in which the low virus titres detected in the tissues were cleared. After infection, interferon (IFN)-gamma synthesis in A/J- mice was lower than that in A/J+ and A/J mice; IFN-gamma synthesis was very high in BALB/c+ and BALB/ci mice, but low in BALB/c- mice. Studies of the anti-MHV3 effect induced in macrophages in vitro showed that only IFN-gamma-activated A/J mouse macrophages were able to restrict partially the growth of MHV3, regardless of whether the animals had been immunized. The effect occurred only when the cells were activated with IFN-gamma before virus infection. The results indicate that the resistance of A/J mice to our strain of MHV3 is not natural but is acquired after immunization, and that the mechanism involved is dependent on T cell activity, IFN-gamma production and the sensitivity of macrophages to IFN-gamma.
Lucchiari
M A
MA
Instituto Butantan, Laboratorio de Immunologia Viral, Sao Paulo, Brasil.
Martin
J P
JP
Modolell
M
M
Pereira
C A
CA
D000818:Animals; D002478:Cells, Cultured; D004198:Disease Susceptibility; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000254:growth & development / Q000302:isolation & purification; D013045:Species Specificity
D007371:Interferon-gamma