Altered expression of a novel cellular gene as a consequence of integration of human T cell lymphotropic virus type 1.

By analysing a genomic DNA clone derived from the human T cell lymphotropic virus type 1 (HTLV-1)-infected cell line, TL-Su, we found that an integrated HTLV-1 provirus interrupted the poly(A) signal-containing exon of a novel gene, RY-1. Nucleotide sequence analysis of a cDNA derived from Jurkat cells revealed that the normal RY-1 mRNA could encode a novel protein that has an unique primary structure, suggesting that a nucleic acid binding property was involved. Proviral integration led to an accumulation of aberrant RY-1 mRNA species in the cells. All the aberrant RY-1 cDNAs derived from TL-Su cells terminated at the poly(A) site of the R region of the HTLV-1 long terminal repeat and initiated in the intron, approx. 800 bp upstream from the putative second exon. Furthermore, another intron, downstream from this position, remained unspliced in some of the cDNAs. In addition to the activation by the integrated viral elements of cryptic promoters located upstream, mechanisms involving altered rates of degradation or transport from the nucleus to the cytoplasm of intron-containing RNA were suggested.