Intron-oriented HTLV-1 integration in an adult T-cell leukemia/lymphoma cell line sustains expression of intact ift81 mRNA.

Abstract

The oncogene hbz in human T-cell leukemia virus type 1 (HTLV-1) is encoded on the antisense strand, generating spliced and unspliced transcripts. We investigated splicing regulation in the context of cellular splice donors and the hbz splice acceptor when integrated within the host chromosomal DNA. In ATL cell line ED, the HTLV-1 provirus integrated into the 10th intron of the gene ift81, aligning transcriptionally with ift81. Both genes were actively transcribed, yielding ift81-hbz chimeric mRNA but not hbz-ift81. Splicing efficiency from the 10th exon of ift81 to the 2nd exon of hbz was 24.2% at most, suggesting reduced function of hbz splice signals on ift81-driven transcripts. This stochastic regulation may minimize disruption of cellular gene expression by proviral integration, potentially promoting survival of HTLV-1-infected cells and contributing to HTLV-1 pathogenesis.