A 3' end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus

Abstract

Nondefective Friend helper murine leukemia virus (Fr-MuLV) induces primarily erythroleukemias in NFS mice, whereas Moloney murine leukemia virus (Mo-MuLV) induces T cell lymphomas. Using molecular clones of these two viruses, we constructed a recombinant in which a 0.62-kilobase fragment encompassing the U3 region at the 3' end of the Fr-MuLV genome replaced the corresponding region of Mo-MuLV. The recombinant virus obtained by transfection of this clone, whose genome is derived primarily from Mo-MuLV, induces almost exclusively erythroleukemias in NFS mice. This and the previous result of Chatis et al. (Proc. Natl. Acad. Sci. U.S.A. 80:4408-4411), showing that the reciprocal recombinant whose genome is primarily derived from Fr-MuLV induces almost exclusively lymphomas, argue that a strong determinant of the distinct disease specificities of Fr-MuLV and Mo-MuLV lies in this 3' end 0.62-kilobase fragment which contains the putative virus enhancers. To more precisely define this determinant, we have begun to construct recombinants in which smaller 3' end fragments of the Fr-MuLV and Mo-MuLV genomes are exchanged. Analysis of the first such recombinant showed that Fr-MuLV can be converted to a lymphoma-inducing virus in NFS mice by substitution of a 0.38-kilobase fragment encompassing the virus enhancers in U3 with the corresponding region of the Mo-MuLV genome.