Studies have been aimed at trying to understand mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more of the stages of the malignant process. Investigations on the acute erythroleukemia-inducing virus, spleen focus-forming virus (SFFV), have concentrated on determining which viral sequences are responsible for pathogenicity and erythroid cell specificity. Our data have shown that sequences in the long terminal repeat (LTR) region of SFFV do not determine the erythroid cell tropism of the virus and that expression of the SFFV env gene in the absence of other SFFV genes and the SFFV LTR is pathogenic. Thus, the primary effect of SFFV on erythroid cells, which is to alter the requirement that the cells have for the erythroid hormone erythropoietin, is due to the product of its env gene. To further understand how the viral env gene product may do this, we have been studying variants of the virus, SFFV-P and SFFV-A, which both induce acute erythroleukemia in mice but differ in their effects on erythroid cells as well as in the post-translational modification of their env gene products. By making recombinants between SFFV-P and SFFV-A, we have been able to localize the sequences responsible for the biological and biochemical differences between these two viruses to a 678 bp region in the 3' region of the envelope gene. Studies on the genetics of susceptibility to early erythroleukemia induced by Friend murine leukemia virus are concentrating on a gene previously identified on chromosome 5 that encodes a viral envelope protein related to that of mink cell focus-inducing virus. Attempts are being made to confer resistance to leukemia by genetic transfer of this gene as well as to apply this mouse model for resistance to the treatment of human diseases such as AIDS.
