1887

Abstract

Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate–early gene expression in HTLV-I-infected cells and its regulation by Tax. was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the gene promoter in a transient transfection assay. A series of deletion and mutation analyses of the gene promoter indicated that a 35 bp region immediately upstream of the TATA-box sequence, which contains a consensus cAMP response element (CRE) and a G+C-rich sequence, is the critical responsive element for Tax activation. Site-directed mutagenesis analysis of the 35 bp region suggested that both the consensus CRE motif and its upstream G+C-rich sequence were critical for Tax transactivation. Electrophoretic mobility shift analysis (EMSA) using the 35 bp sequence as probe showed the formation of a specific protein–DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein–DNA complex. These results suggested that Tax directly transactivated gene expression, mainly through a CRE sequence via the CREB transcription pathway.

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2003-12-01
2019-10-21
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