Nucleic acid sequences of the oncogene v-rel in reticuloendotheliosis virus strain T and its cellular homolog, the proto-oncogene c-rel

K C Wilhelmsen, K Eggleton, H M Temin
1984 Journal of Virology  
Reticuloendotheliosis virus strain T (Rev-T) is a highly oncogenic replication-defective retrovirus which contains the oncogene v-rel. It is thought that Rev-T arose when a virus similar to Rev-A, the helper virus of Rev-T, infected a turkey and recombined with c-rel from that turkey. There is one large c-rel locus in the turkey genome which contains all of the sequences homologous to v-rel (K. C. Wilhelmsen and H. M. Temin, J. Virol. 49:521-529, 1984). We have sequenced v-rel and its flanking
more » ... equences, each of the regions of the c-rel locus from turkey that are homologous to v-rel and their flanking sequences, and the coding sequence for env and part of pol of Rev-A. The v-rel coding sequences can be translated into a 503-amino acid env-v-rel-out-offrame-env fusion polypeptide. We have not detected any sequences in the Los Alamos or University of California-San Diego data bases that are more significantly related to the amino acid or nucleic acid sequence of v-rel than to the randomized sequence of v-rel. Comparison of Rev-A, Rev-T, and c-rel indicates that the v-rel sequences may have been transduced from the c-rel (turkey) locus by a novel mechanism. There are sequences in Rev-A and c-rel that are similar to splicing signals, indicating that the 5' virus-rel junction of Rev-T may have been formed by cellular RNA splicing machinery. Eight presumed introns have presumably been spliced out of c-rel to generate v-rel. There are also short imperfect regions of homology between sequences at the boundaries of v-rel and sequences in Rev-A and c-rel (turkey), indicating that c-rel may have been transduced by homologous recombination. There are many differences between the amino acid sequences of the predicted translational products of v-rel and c-rel which may account for their difference in transformation potential. These sequence differences between v-rel and c-rel include 10 missense transitions, four missense transversions, and three places where Rev-T has a small in-frame deletion of sequences relative to c-rel. Most of the coding sequence differences between c-rel and v-rel are nonconservative amino acid changes. * Corresponding author. 172 gene appears to be the result of a quantitative difference in the level of their expression (13, 30). We have been studying the highly oncogenic retrovirus reticuloendotheliosis virus strain T (Rev-T), which contains the oncogene v-rel. Rev-T was first isolated from a turkey (28). It is thought that Rev-T arose when a virus similar to Rev-A infected a turkey and recombined with c-rel from that turkey. Analysis of molecular clones of proviruses of Rev-T and Rev-A (Rev-A is the nondefective helper virus of Rev-T) shows that in Rev-T, v-rel is substituted for most of env in Rev-A (see Fig. 1) (3, 8, 18 ). Rev-T also has a large deletion of sequences which encode much of gag and pol in Rev-A. This deletion is necessary for transformation of cells by v-rel (4). In Rev-T-infected cells, there are two viral RNA transcripts that contain v-rel sequences: a full-length genomic size transcript and a subgenomic RNA transcript which is similar in size to the subgenomic env mRNA in Rev-A (32; K. C. Wilhelmsen, unpublished data). The subgenomic vrel-containing transcript in Rev-T-infected cells is thought to be translated to make the v-rel gene product. The positions of the subgenomic env mRNA splicing sequences in Rev-A are shown in Fig. 1 (32; Wilhelmsen, unpublished data). To determine the nature of the v-rel gene product and to determine whether it is expressed as a fusion product with viral genes, we sequenced v-rel and its flanking sequences in Rev-T as well as the 3' half of Rev-A. We wanted to determine (i) whether the acquisition of the rel sequences was by the recombination mechanism postulated for other oncogenes, (ii) whether all of the v-rel-specific sequences in Rev-T came from the previously identified c-rel turkey locus
doi:10.1128/jvi.52.1.172-182.1984 fatcat:qc5nymcl5fdnxabkq2rneonkdy