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 mile disease in which the low virus titres detected in the tissues were cleared. After infection, interferon (IFN)-γ synthesis in A/J-mice was lower than that in A/J+ and A/Ji mice; IFN-γ 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-γ-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-γ 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-γ production and the sensitivity of macrophages to IFN-γ.
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