Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses.

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Abstract
To probe the genetic basis of disease specificity of nondefective murine type C viruses, recombinants were constructed in vitro between molecular clones of Friend murine leukemia virus (Fr-MuLV) and Moloney murine leukemia virus (Mo-MuLV). Fr-MuLV induces erythroleukemias when injected into newborn NFS mice; Mo-MuLV almost invariably induces T-cell lymphomas. A recombinant whose genome is derived primarily from Fr-MuLV but which has 621 nucleotides of Mo-MuLV information at its 3'' end induces almost exclusively thymic lymphomas. The sequences derived from Mo-MuLV include 99 nucleotides encoding the carboxyl terminus of Prp15E, the origin of DNA +-strand synthesis, all of the U3 region, and 36 nucleotides of the R portion of the long terminal repeat. When the segment of Mo-MuLV was removed and replaced with the comparable segment from Fr-MuLV, the virus was again erythroblastosis-inducing. Evidently, transcriptional signals in U3 may determine tissue tropism and hence influence disease specificity (targeting) of murine leukemia viruses.