Natural resistance of mice to mouse hepatitis virus type 3 infection is expressed in embryonic fibroblast cells

Abstract

Mouse hepatitis virus 3 (MHV3) infection in mice varies according to the mouse strain used; they may show resistance, semi-susceptibility (paralysis) or full susceptibility (lethal acute hepatitis). In order to study the mechanism of inborn resistance, viral infection was carried out in primary cultures of embryonic fibroblasts originating from various mouse strains exhibiting different sensitivities to MHV3 infection. Virus-induced cytopathic effects and cell membrane antigens as well as virus replication and interferon synthesis were studied. Persistent infection was induced in four out of six primary embryonic fibroblast cultures and in six of six secondary cultures. Two primary embryonic fibroblast cultures from susceptible strains underwent total lysis. A high yield of virus was obtained, as tested by viral titres and cell membrane antigen detection. No significant difference in virus production or in interferon synthesis was observed in fibroblast cultures of the various mouse strains tested. Cytopathic effects characterized by cell lysis were related, however, to phenotypes in vivo. This effect was lost after a single trypsinization of the culture. In addition, resistance to virus-induced cell lysis was inhibited by actinomycin D treatment. These results indicate that the intrinsic resistance of fibroblasts is effective not against virus replication but against virus-induced cell lysis. Such a cellular control mechanism may be an important factor for resistance in vivo.