Transcriptional modulation of a flanking gene by HTLV-1 integration, and demonstration of a cellular transcript homologous to HTLV-1 LTR-gag region
نویسندگان
چکیده
SUMMARY : We have cloned a human T-lymphotropic virus type-1(HTLV-1) pro-viral • @ genome, ƒÉ 255 • @ M, • @ of • @ a • @ cell • @ line, • @ TL-Su, • @which • @ has • @ been • @ established • @ from • @ peripheral • @ blood • @lymphocytes • @ of • @ a • @ healthy • @HTLV-1 • @carrier. • @ The ƒÉ 255 • @ M • @ had • @ a • @ very • @ similar restriction • @ map • @ to • @ that • @ of • @ a • @ previous • @isolate, ƒÉ ATK-1, • @but • @ a • @ different • @junctional • @ repeat , TGAAAG, consistent with the random integration sites of HTLV-1. We found two species of interesting cellular gene transcripts. The first gene homologous to LTR-gag region of HTLV-1 was expressed as 4.5 kb RNA only in the cells of lym-phoid cell lineage as far as tested. The RNA was present even in uninfected cells including a T-cell line, Jurkat, and a B-cell line, FLEB-12-3-4, but not in another T-cell line, CEM. Because of strong viral RNA signals, we could not demonstrate the RNA in virus producing cell lines. The results suggested the presence of human cellular gene related with LTR-gag region of HTLV-1. The other gene homologous to 5' flanking • @gelle • @of • @ the ƒÉ 255 • @ M • @ was • @expressed • @ as • @1.8kb • @ mRNA • @ in • @ all • @human • @ cells • @tested • @ except for the TL-Su cell. In the TL-Su cell, HTLV-1 integration modulated this gene transcription into 3.8, 3.2. 2.0 and 1.6kb mRNAs qualitatively, and at least 10 times more than other human cells quantitatively. The data suggests that HTLV-1 gene integration may cause the transcriptional modulation of cellular genes by insertional mutagenesis.
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