An immunological analysis of natural resistance to mouse hepatitis virus (JHMV strain) infection in C3H mice.

1. Since the development of resistance against mouse hepatitis virus (JHMV strain) coincides with the maturation of the immune system, we studied the possible role of distinct immunological components in the resistance of adult mice during JHMV infection. 2. Adult C3H mice naturally resistant to JHMV were rendered susceptible to infection by lethal 60Co-irradiation and were subsequently reconstituted with limiting numbers of syngeneic bone marrow cells or spleen cells. 3. Resistance or susceptibility depended on the number of cells used for reconstitution and the interval between reconstitution and infection. Spleen cells from suckling mice affected neither resistance nor susceptibility and peritoneal cells from adult mice and thymus cells reduced resistance. Persistence of JHMV was demonstrated by virus reactivation. 4. Animals infected with JHMV only once before being rendered immunoincompetent showed a different pattern of resistance. One to four months after infection, 15 to 35% of the animals died after reconstitution without having been reinfected, and persisting JHMV was found in their liver, spleen and peritoneal exudate. The survivors (47 to 87%) were resistant to further JHMV infection during immunodeficiency. 5. Animals immunized 3 times with JHMV before irradiation did not show virus reactivation and were fully resistant to JHMV reinfection after reconstitution. The level of neutralizing anti-JHMV serum antibodies in the group of mice immunized only once was comparable with the level of those immunized 3 times. 6. The role of macrophage activation and cell-mediated immunity in this model are discussed as an explanation for the resistance to, and persistence of, JHMV.