Naturally Occurring Leukemia Viruses in H-2 Congenic C57BL Mice. I. High Lymphoma Incidence Following Milk-borne Transmission of Virus

Two modes of transmission of ecotropic type C viruses occur naturally in C57BL mice: maternal (i.e., through milk) and genetic. By selection of virus-positive and virus-negative B10.ASgSn [B10.A (H-2a)] mothers and foster-nursing of C57BL/10ScSn [B10 (H-2b)] newborns, four sublines of C57BL mice were obtained: B10.A V+, B10.A V-, B10 V+, and B10 V-. (V+ denotes positive for milk-transmitted B-tropic virus; V- denotes negative for milk-transmitted B-tropic virus). Milk transmission of naturally prevalent B-tropic virus (V+ sublines) led to persistent infection of all offspring over at least 8 generations. Milk transmission of virus was associated with a very high incidence of lymphomas. The H-2 complex influenced the titers of virus after milk transmission, which were higher in B10.A V+ mice than in B10 V+ mice. H-2 control of virus titers, as measured by serum p30 assay, was confirmed in (B10.A V+ X B10 V+)F2 mice. Resistance to the virus was dominant, because serum p30 levels in F1 and H-2a/b F2 animals were similar to those in the B10 V+ subline and lower than those in the B10.A V+ subline. The H-2 complex also influenced the incidence of lymphomas (78 and 42%, respectively, in the B10.A V+ and B10 V+ sublines). Most B10.A V+ lymphomas were of T-cell origin, whereas most B10 V+ lymphomas were classified as non-T/non-B cells. Genetic transmission of virus (V- sublines) led to heterogeneous expression of both N- and B-tropic viruses, which thereby established the mottled trait for expression of genetically transmitted type C viruses in C57BL mice. Genetic transmission was associated with a low incidence of lymphomas that occurred in senescence.