494 Resistance to Friend Helper Virus Erythroblastosis

Progress in understanding steps in viral leukemogenesis has often come from the study of mouse strains resistant to the development of leukemia. This approach has led to the identification of mouse genes controlling replication of input leukemia viruses (Fv-1 [1], Fv-4 [2]), replication of defective transforming viruses (Fv-2 [3, 4]), susceptibility to virus-induced immunosuppression (Fv-3 [5]), and immune response to virus or leukemic cell antigens (H-2 [6], H-2-1inked genes Rfv-1 [7] and Rfv-2 [8], and non-H-2-1inked Rfv-3 [9]). Friend virus complex consists of a replication-competent murine leukemia virus designated Friend helper virus or F-MuLV, l and a replication-defective spleen focus-forming virus designated SFFV (10, 11). In addition, some pools of Friend virus contain recombinant mink cell focus-forming virus(es) designated F-MCF. While SFFV is required for the rapid induction of erythroblastosis in adult mice (12, 13), the pathogenicity of F-MuLV and F-MCF is less clear. Early reports using uncloned virus (10, 14, 15) indicated that Friend virus pools lacking SFFV caused lymphoma in BALB/c mice (16, 17), or a disease with characteristics of lymphoma and erythroblastosis in Swiss mice (10). More recent experiments using virus cloned by endpoint dilution in tissue culture (18, 19), or molecularly cloned virus (20), show that NFS/N and BALB/c mice inoculated with F-MuLV as neonates develop erythroblastosis. In contrast, mice of other strains, including DBA/2 and C57BL, are resistant to F-MuLV erythroblastosis (21); a recent report indicates that DBA/2 mice develop lymphoma and myelogenous leukemia several months after neonatal infection with F-MuLV (22). The DBA/2 resistance to erythroblastosis acts like a single dominant gene in backcrosses to NFS/N (21) and BALB/c (22). DBA/2 mice carry a dominant gene on chromosome 5 that restricts the replication of MCF viruses (23), and this gene, designated Rmcf, appears to be responsible for the DBA/2 resistance to F-MuLV erythroblastosis (J. W. Hartley and W. P. Rowe, unpublished observations). However, in the same assay system, C57BL mice do not restrict the growth of MCF virus, i.e., they carry the Rmc~ allele (23). It was therefore of interest to investigate the basis of resistance to F-MuLV erythroblastosis in C57BL mice. The experiments reported here show that C57BL mice, although resistant to F-MuLV erythroblastosis, develop lymphoma and myelogenous leukemia after a