Using mouse model systems, studies have been carried out to determine how non-oncogene-containing retroviruses cause erythroleukemia and why certain mice are resistant to the pathogenic process. The Friend spleen focus-forming virus (SFFV) causes a rapid erythroleukemia due to the unique envelope gene that it carries. The SFFV envelope glycoprotein alters the growth of erythroid cells by rendering the cells independent of the erythroid hormone erythropoietin (Epo). In order to determine whether the SFFV envelope glycoprotein is activating the Epo signal transduction pathway, studies were carried out to compare erythroid cells stimulated with Epo or infected with SFFV for expression of tyrosine- phosphorylated proteins and DNA-binding proteins. Both Epo and SFFV were shown to induce the tyrosine phosphorylation of several common substrates, one of which appears to be a DNA-binding protein related to the class of transcription factors designated STAT proteins. No differences could be detected in the Epo signal transduction pathways between strains of mice that are resistant or susceptible to the effects of SFFV. Studies were also carried out on a mouse resistance gene, Rmcfr, that prevents the development of erythroleukemia induced by Friend murine leukemia virus (F-MuLV). It was previously shown that F-MuLV- induced erythroleukemia requires the generation and replication of polytropic MuLVs. Molecular cloning of the Rmcf resistance gene now indicates that it is the envelope gene of an endogenous modified polytropic virus. Expression of this gene apparently blocks infection of polytropic MuLVs by a mechanism analogous to viral interference.
