Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity

We have previously shown that noninfected human T-cell lines express the canonical 5.7 kb mRNA coding for the type beta platelet-derived growth factor-receptor (PDGF beta-receptor), whereas HTLV-I-infected T-cell lines express a novel PDGF beta-receptor mRNA of 3.8 kb, In this report, we have extended those studies to molecularly characterize the 3.8 kb PDGF beta-receptor mRNA and show that it has resulted from integration of an apparently undeleted HTLV-I provirus into the PDGF beta-receptor gene in an orientation enabling expression of a truncated PDGF beta-receptor mRNA using the 3' HTLV-I long terminal repeat as a promoter, Further, NIH3T3 cells transfected with a plasmid containing the truncated PDGF beta-receptor ORF plasmid generate colonies in soft agar with more cells per colony than untransfected cells, or cells transfected with the Tax 1 or PDGF-B (c-sis) plasmids, These results indicate that the truncated PDGF beta-receptor protein acquires transforming capability and that HTLV-I-induced truncation of PDGF beta-receptor may correlate with HTLV-I-associated neoplasia of human T-cells.