Partial nucleotide sequence of Rous sarcoma virus-29 provides evidence that the original Rous sarcoma virus was replication defective.

Rous sarcoma virus-29 (RSV-29) is the strain of RSV that has the least number of passages beyond its isolation from chicken tumor no. 1 among all current strains of RSV. Biological characterization indicated that it was replication defective. RNA analysis of nonproducer clones of RSV-29-infected chicken embryonic fibroblasts showed the presence of a subgenomic message of 2.6 kilobases containing src and a genomic RNA of 7.7 kilobases that contains gag, pol, and src, but not env. The src-containing EcoRI fragment of RSV-29 proviral DNA was molecularly cloned. Sequence analysis of the regions flanking src revealed that the env gene was completely deleted in RSV-29 and that the sequence across the deletion was exactly the same as the Bryan high-titer strain of RSV. The sequence immediately 3' to src in RSV-29 was closely related to that of the Prague strain of RSV. The fact that the strain of RSV which has the minimal number of passages beyond its isolation is replication defective supports the hypothesis of Lerner and Hanafusa (J. Virol. 49:549-556, 1984) that the original RSV is a defective transforming virus. This defective transforming virus is postulated to be the precursor to other defective RSVs like the Bryan high-titer strain and to nondefective RSVs like the Prague strain. The particular clone of RSV-29 that we studied also had a short stretch of sequence duplication at the 3' end of the pol gene, which was presumably created by an error of reverse transcription.