ABELSON LEUKEMIA VIRUS TRANSFORMATION

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A large number of retroviruses induce tumors at high frequency when injected into appropriate hosts. Most of these viruses act by directly interfering with normal cellular growth and differentiation and, because they also transform cells in vitro, the cell-virus interactions can be studied under controlled conditions. Nearly all of these transforming viruses carry gene(s) derived from normal cellular DNA called onc genes that encode the proteins that are responsible for cellular transformation. Because onc genes are derived from normal cellular DNA, understanding their mode of action in a viral system would be an important step toward understanding their role, not only in oncogenesis but also in normal growth and development. We are examining this question using a Abelson virus (A-MuLV) model system and a genetic approach. A-MuLV transforms some fibroblast of lymphosarcomas in mice. Through the isolation of variant A- MuLV strains, it has been possible to separate viral functions required for fibroblast and lymphoid transformation as well as those required for high efficiency lymphoid transformation in vitro and in vivo. We plan to use these mutants and isolate others to determine the mechanism(s) that control A-MuLV-cell interaction.