Tissue tropism of a leukemogenic murine retrovirus is determined by sequences outside of the long terminal repeats.

Although it has been previously determined that the long terminal repeat (LTR) sequences of several murine retroviruses specify the major tissue tropism of leukemias they induce, data reported here show that the LTR is not responsible for tissue tropism in the case of all leukemogenic viruses. In an effort to determine whether LTR sequences of the acute erythroleukemia-inducing spleen focus-forming virus (SFFV), like those of the other murine leukemia viruses, are uniquely required to confer tissue specificity to the virus, we prepared recombinant SFFVs in which the LTR region containing promoter and enhancer functions was replaced with analogous LTR regions from Friend and Moloney ecotropic and mink cell focus-inducing viruses. It was found that all of the SFFV constructs, even those with a LTR derived from lymphoma-inducing viruses such as Moloney murine leukemia virus, transformed erythroid cells in vitro and induced exclusively an erythroid disease. These results demonstrate that sequences in SFFV that determine the tissue-specific nature of the disease reside outside the LTR.