Persistent in vitro infection with mouse hepatitis virus 3.

Mouse hepatitis virus 3 (MHV3) infection in mice displays various types of sensitivity according to mouse strains: resistance, full susceptibility and semisusceptibility . MHV3 infections were carried out in primary cultures of embryonic fibroblasts originating from various mouse strains and in mouse lymphoid cell lines. Persistent infection was induced in 2 out of 3 primary embryonic fibroblast cultures. A high production of virus was obtained, as tested by viral titers and cell membrane antigen detection. Cytopathic effects characterized by cell lysis were related to in vivo phenotypes. Persistent MHV3 infection established in vitro in YAC mouse lymphoid cell line was characterized by virus production, occurrence of cellular viral antigens and cell lysis. Cell cloning and antibody treatment experiments indicated that the type of viral transmission was horizontal and not vertical. These data indicate that persistent infection induced by MHV3 in lymphoid cell lines is characterized by a viral "carrier state" where production of infectious viral particles remains in equilibrium with cell permissiveness. Biological and biochemical properties of MHV3 variants derived from persistently infected YAC lymphoid cells were characterized. Similar heterogeneous thermosensitive properties were observed when YAC-derived cloned substrains (YAC-MHV3) were compared to parental-derived cloned viruses, indicating that no selection of temperature-sensitive mutants was induced in persistently infected YAC cells. The capacity, however, of YAC-MHV3 to induce a lethal acute disease when injected into susceptible mice was lost very rapidly and seemed to be regulated by host factors.