TRANSFORMING VARIANTS OF THE AVIAN MYC-CONTAINING RETROVIRUS FH3 ARISE PRIOR TO PHENOTYPIC SELECTION

The avian retrovirus FH3, which encodes a Gag-Myc fusion protein, tran sforms chicken macrophages but not fibroblasts. However, passage of FH 3 viral stock in fibroblasts leads to emergence of a virus capable of fibroblast transformation. This virus has not acquired myc mutations; instead, it carries internal gag deletions which confer the ability to transform fibroblasts. We now demonstrate that this and similar delet ion variants emerge repeatedly during selection. Sequence analysis rev eals direct repeats at or near deletion junctions, suggesting that err ors during reverse transcription may be involved in genesis of these v iruses, which are then positively selected in fibroblast culture. By u sing the polymerase chain reaction, we found that such variants preexi sted in original stocks even before selection, although they could not be detected by focus assay.