Incidence and phenotypic heterogeneity of Moloney virus-induced leukemias: a multigenic control

The incidence of leukemias was established in mice of different inbred strains inoculated with Moloney leukemia virus (M-MuLV), and a complex genetic control was found. To characterize the different steps of the host-virus relationship further, the degree of viremia, the appearance of leukemia, organ involvement, and the surface phenotype of leukemic cells were studied in individual mice. The results demonstrate that: a) The viremia was controlled by H-2 and non-H-2 genes. Three H-2 genes located in the I and D or T region of the MHC behave like immune-response genes controlling the specific antiviral immune response. Other gene(s) mapped outside the complex also affected the virus production. Both sets of genes influenced leukemia incidence, since leukemias were observed only in highly viremic strains. b) Additional non-H-2 genes, which were not involved in viremia control, were determinants in the induction of malignancies because some sensitive strains do not become leukemic despite high levels of viremia. c) The anatomical type of Moloney virus-induced leukemias varied according to the non-H-2 background. Most of the leukemias arising in B10 congeneic mice involved the thymus and were frequently limited to this organ, whereas BALB mice preferentially developed splenic leukemias. d) In a given inbred strain, the leukemias arising in different animals frequently expressed different phenotypes. It can be concluded that Moloney virus-induced leukemia is a multistep process, viral production being necessary but not sufficient in and of itself to induce a malignant transformation.