Mutational analysis of v-rel, the oncogene of reticuloendotheliosis virus strain T.
Reticuloendotheliosis virus strain T (Rev-T) is a highly oncogenic retrovirus that induces a lethal lymphoma in young galliform birds and also transforms and immortalizes avian lymphoid cells in vitro. Rev-T presumably arose when a reticuloendotheliosis virus (Rev) incorporated a portion of the turkey c-rel gene into its genome, forming the v-rel oncogene. The predicted v-rel protein (p59v-rel) has 14 amino acid substitutions and 3 amino acid deletions relative to the predicted turkey c-rel protein. The 5' Rev env-derived amino-terminus of p59v-rel also has amino acid substitutions in codons 3, 6, and 9 relative to wild-type Rev-A env. To distinguish the critical alterations from the neutral ones, we made a mutation that resulted in a substitution of the 5' Rev env-derived amino-terminus by a single methionine, as well as several back-mutations, in the context of an otherwise wild-type v-rel and tested the transforming, immortalizing, and tumorigenic properties of the resulting proteins. All proteins tested retained the transforming, immortalizing, and tumorigenic functions of v-rel. Absence of the 5' Rev env-derived amino-terminus, as well as back-mutations of six of the amino acid changes present in the rel-derived amino-terminal and central regions of v-rel, reduced transformation efficiency. The mutations present in codons 3, 6, and 9 of p59v-rel showed complicated interactions in their activating effects on transformation efficiency. We also showed that loss of the immortalizing function did not abolish tumorigenesis by v-rel. We further showed that the primary transduction event involving the turkey c-rel gene could have occurred with a replication-competent Rev having v-rel-specific mutations in codons 3, 6, and 9 of the env gene.
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002642:Chick Embryo; D002645:Chickens; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015752:Genes, env; D008206:Lymphatic Diseases / Q000382:microbiology*; D008969:Molecular Sequence Data; D009154:Mutation; D020572:Oncogene Proteins v-rel; D009857:Oncogenes; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014170:Transformation, Genetic
D004279:DNA, Viral; D020572:Oncogene Proteins v-rel; D011506:Proteins; D015682:Retroviridae Proteins, Oncogenic