DIFFERENTIAL BEHAVIOR OF THE MO-VIRUS IN RATS AND MICE(PYF101 ENHANCER VARIANT OF MOLONEY MURINE LEUKEMIA)

The Mo+PyF101 enhancer variant of Moloney murine leukemia virus (M-MuL V) has been very useful in investigating M-MuLV leukemogenesis. When i noculated subcutaneously (sc) into neonatal mice, Mo+PyF101 M-MuLV is attenuated for development of disease. Previous studies in mice infect ed with wild-type M-MuLV have revealed several important preleukemic e vents, including development of splenic hyperplasia, defects in bone m arrow hematopoiesis, and in vivo generation of MCF viruses that arise by recombination in the uninfected mouse. Mo+PyF101 M-Mu LV is defecti ve in inducing these effects after sc inoculation. In the experiments reported here, a study of Mo+PyF101 M-MuLV infection in rats was carri ed out. Wild-type M-MuLV is leukemogenic in rats, but infected rats do not form MCF recombinants since they lack the necessary endogenous po lytropic envelope sequences. Since Mo+PyF101 M-MuLV's leukemogenic def ect is correlated with a failure to generate MCF recombinants, it seem ed possible that wild-type M-MuLV might not have a leukemogenic advant age over Mo+PyF101 M-MuLV in rats, where MCF recombinants cannot form. Neonatal Fisher F344 rats were inoculated sc or intraperitoneally by wild-type and Mo+PyF101 M-MuLVs. Surprisingly, Mo+PyF101 M-MuLV was co mpletely deficient in leukemogenesis in rats when inoculated by either route while wild-type M-MuLV induced lymphoma with the predicted time course. The leukemogenic defect for Mo+PyF101 M-MuLV resulted from a pronounced defect for establishing infection in rats. Further studies of wild-type M-MuLV in rats indicated that infection was confined almo st exclusively to the thymus at early times. In mice wild-type M-MuLV establishes substantial infection in other hematopoietic organs such a s spleen and bone marrow as well. Thymic infection was also correlated with a decrease in thymic cellularity at early times. (C) 1998 Academ ic Press.