FILTERABLE AGENTS AND TUMOR INDUCTION IN MICE

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The Friend leukemia viruses are a family of variant viruses that induce similar but not identical patterns of disease. The wild type causes an erythroleukemia in adult mice, either associated with anemia (FLV-A) as was the original isolate, or with polycythemia (FLV-P). The FLV-P strains consist of a complex of FLV-A, the defective spleen focus-forming virus (SFFV) and additional genetic components of endogenous mus sequences. These variant viruses may have emerged as a result of recombinant events. We plan a comparative study of the molecular properties and biological activities of the leukemogenic FLV-A and FLV-P virus strains produced in vivo in the leukemic mouse, and the attenuated virus produced in vitro by our chronically infected erythroleukemia cell lines. The integrated and free viral DNA of each strain will be characterized by restriction enzyme analysis. Using FLV and SFFV probes obtained from different laboratories and probes from clone virus of our strains, the integration patterns and the expression of the viral genome will be examined. The level of methylation of the pro-viral and viral genes will aso be investigated, since gene activity may be influenced by the degree of methylation. We will also seek to define the role of the virion protein kinase and endonuclease. In characterizing the RNA, protein and enzymatic activities of the purified virions, we hope to obtain a profile which will identify each strain. This would be extremely useful in comparing alterations in the properties of the infecting virus with that of the virus recovered from the leukemic animal, in view of the readiness with which recombination occurs with components of endogenous viruses of the cell. It may also be possible to associate these changes with changes in malignant potential. Information sought from this proposed work can be of potential significance to explain the molecular basis of leukemogenicity. A better understanding of the mechanisms involved in the development of leukemia is fundamental for the prevention and treatment of the disease.