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HTLV-1 bZIP factor suppresses c-Fos transcription and impairs T cell activation

c-Fos forms AP-1 heterodimer with JUN family proteins such as c-Jun and functions as a transcription factor to regulate diverse biological processes including T cell activation. Although an HTLV-1-encoded oncoprotein Tax induces the expression of c-fos, its expression is significantly down-regulated in fresh ATL cells compared with CD4+ T cells of healthy donors. In this study, we found that HTLV-1 bZIP factor (HBZ) is responsible for the suppressed c-fos transcription in ATL cells. The results of reporter assay implied the roles of LXXLL motif of HBZ on the suppression of c-fos. HBZ has been reported to suppress AP-1 and NFAT signaling pathways through the direct interaction with c-Jun and NFATc2, respectively. We found c-Fos overexpression impairs the suppressive effects of HBZ on AP-1 and NFAT, suggesting that HBZ overcomes the inhibitory effects of c-Fos by suppressing its transcription. HBZ is known to bind to c-Jun instead of c-Fos. Suppressed transcription of c-fos facilitates HBZ to interact with c-Jun, and enhances suppressive effect of HBZ on AP-1 pathway. AP-1 and NFAT signaling pathways are activated by T-cell receptor (TCR) stimulation, leading to T cell activation. We found that TCR stimulation induces the c-fos up-regulation and the expression of the activation marker CD69 on CD4+ T cells of wild type mice, but not of HBZ transgenic mice, indicating that the activation of the signaling pathways initiated from TCR are suppressed by HBZ. We hypothesize that c-fos suppression by HBZ may contribute to impaired activation of T cells and pathogenesis of HTLV-1 infection.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Kawatsuki, A., Yasunaga, Ji. & Matsuoka, M. HTLV-1 bZIP factor suppresses c-Fos transcription and impairs T cell activation. Retrovirology 11 (Suppl 1), P92 (2014).

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