CIS-ACTIVE ELEMENTS OF FRIEND SPLEEN FOCUS-FORMING VIRUS - FROM DISEASE INDUCTION TO DISEASE PREVENTION

The polycythemic strain of the Friend spleen focus-forming virus (SFFV p) is a replication-defective, acutely transforming retrovirus inducin g a bistage erythroleukemia in susceptible mice. The first stage of th e disease is an acute polyclonal erythroblastosis induced by the proli feration-promoting effect of gp55. gp55 is expressed from a spliced su bgenomic message of SFFVp and stimulates the cellular receptor for ery thropoietin. Using a selectable SFFVp that otherwise mimics the specif icity of the disease, we demonstrate that the kinetics of the polyclon al expansion depends on the transcriptional strength of the retroviral cis-active elements. By exchanging gp55 for apathogenic genes, we sho w that SFFVp enhancer and splice signals can be successfully utilized for the development of retroviral vectors mediating very efficient tra nsgene expression in hematopoietic cells. Apathogenic selectable SFFVp -based vectors carrying distinct enhancer alterations are a valuable t ool to analyze transcriptional control of leukemia viruses in the abse nce of oncogenic proteins. Moreover, they might have therapeutic poten tial.