Fv-2 locus controls expression of Friend spleen focus-forming virus-specific sequences in normal and infected mice

Abstract

We have recently demonstrated that normal hemopoietic cells express RNA sequences that are homologous to sequences specific for the Friend erythroleukemia virus genome [Bernstein, A., Gamble, C., Penrose, D. & Mak, T. W. (1979) Proc. Natl. Acad. Sci. USA 76, 4455-4459]. In this communication, we report that the Fv-2 locus, the major genetic determinant controlling host susceptibility to erythroleukemia induction by Friend leukemia virus, also controls the expression of endogenous sequences related to the replication-defective component of Friend leukemia virus, Friend spleen focus-forming virus (SFFV), in normal uninfected mice. Two independent congeneic pairs of mice [C57BL/6 (B6) and B6.S; B6 and B6.C(H-7(b))], differing only in a small region of the mouse genome including the Fv-2 locus, were used for this purpose. In both cases, molecular hybridization analysis indicated that the presence of SFFV-related RNA sequences in normal mice was associated with the Fv-2(s) allele: bone marrow or spleen cellular RNA from Fv-2(rr) B6 mice contained no detectable SFFV-related sequences, whereas their congeneic Fv-2(ss) pairs contained relatively high levels of these RNA sequences. The absence of these RNA sequences in Fv-2(rr) mice was not due to deletion of these sequences from the DNA of Fv-2(rr) mice. Repopulation of lethally irradiated Fv-2(rr) mice with syngeneic Fv-2(rr) bone marrow cells did not lead to any increase in the levels of these SFFV-related RNA sequences, suggesting that the expression of these sequences is still reduced or inhibited in actively cycling Fv-2(rr) hemopoietic cells. Infection with Friend leukemia virus resulted in the appearance of high levels of RNA homologous to SFFV-specific sequences in the leukemic spleens of B6.S (Fv-2(ss)) mice, whereas these cellular RNA sequences could not be detected in the spleens of Friend virus-infected B6 (Fv-2(rr)) mice. The demonstration that the same gene locus controls both the expression of exogenous SFFV-specific sequences and erythroleukemia induction by Friend leukemia virus suggests that these sequences may be necessary for erythroleukemic transformation. In addition, the finding that the Fv-2 gene locus controls the expression of endogenous SFFV-related sequences suggests that these sequences may also be involved in normal hemopoiesis.