This application proposes experiments in three broad areas of tumor virology: (i) expression of onc genes and onc proteins, (ii) acquisition of cellular onc sequences by retroviruses and (iii) genetic recombination involving onc genes. Onc gene expression will be studied under conditions where cellular transformation does not take place, in macrophages infected with avian sarcoma viruses or with avian erythroblastosis virus and in cellular mutants that are temperature-sensitive for transformation. Control of onc expression will be further examined with an unusual mutant of avian sarcoma virus PRCII that at the nonpermissive temperature shows greatly reduced levels of transformation-specific RNA and with a molecular hybrid of the metallothionein promoter and the viral src gene. The acquisition of cellular onc sequences will be followed with mutant genomes that carry partial onc. The frequently occuring recombination between partial viral myc and cellular myc will be studied with the aim of determining whether cellular myc receives packaging and LTR sequences from a provirus integrated in its vicinity. The ability of PRCII to capture additional fps sequences will be tested and the effects of this capture on pathogenicity will be determined. Several avian sarcomas isolated in the field will be tested for downstream promotion and expression of various onc genes. Recombination of onc genes will be investigated in crosses between src mutants that are located in an avian and in a murine virus respectively. Recombination between the partially homologous onc genes yes and src and src and fps will also be attempted. Viruses containing two onc genes will be constructed and their transforming ability will be characterized.
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