In Vitro Interaction of Mouse Hepatitis Virus and Macrophages from Genetically Resistant Mice

A variant mouse hepatitis virus MHV(C(3)H) to which cultured peritoneal macrophages from both PRI and C(3)H mice were susceptible was isolated from stocks of the MHV(PRI) strain of mouse hepatitis virus. It was cloned on C(3)H macrophage monolayers and killed both adult PRI and C(3)H mice when injected intraperitoneally. This new variant was antigenically indistinguishable from the wild type virus. While the emergence of the variant virus was delayed in the course of infecting C(3)H macrophages with large inocula of MHV(PRI), the second passage grew to a high titer in both cell types without delay. Thus, adaptation to the new host was immediate. Interference, apparently not interferon-mediated, between the two variant viruses may have been the cause for the delay in the emergence of the variant virus. The delayed destruction of C(3)H-cultured macrophages by large inocula of MHV(PRI) uniformly resulted in the emergence of MHV(C(3)H). Whether the new variant emerged as a result of a selection of a pre-existing stable mutant or was conditioned by "growth" in the resistant host was not determined.