Acquired immunity of A/J mice to mouse hepatitis virus 3 infection: dependence on interferon-? synthesis and macrophage sensitivity to interferon-?

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)-7 synthesis in A / J mice was lower than that in A/J+ and A/Ji mice; IFN-~ synthesis was very high in BALB/c+ and BALB/ci mice, but low in BALB/cmice. Studies of the antiMHV3 effect induced in macrophages in vitro showed that only IFN-7-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-7 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-7 production and the sensitivity of macrophages to IFN-~,.