Activation of oncogenic transcription factor AP-1 in T cells infected withhuman T cell leukemia virus type 1

Human T cell leukemia virus type 1 (HTLV-1) Tax protein transforms primary human T cells in vitro. We previously showed that Tax induces the expressio n of various family members of the transcription factor AP-1 such as c-Jun, JunD, c-Fos, and Fra-1 at the mRNA level in T cells. In this study, we hav e examined the ability of Tax to activate transcription through the AP-1-bi nding site (AP-1 site). A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line , whereas any combination of AP-1 proteins did so much less than Tax, indic ating that the activation of the AP-1 site by Tax may require a mechanism o ther than the induction of AP-1 mRNA. Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activ ity, whereas no normal individuals did. However, the NTLV-1 genes, includin g tax, are not significantly expressed in fresh leukemia cells from ATL pat ients. Our present results suggest that activation of AP-1 occurs through T ax-dependent and -independent mechanisms in HTLV-1-infected T cells, which may play some roles in dysregulated phenotypes of HTLV-1-infected cells.