TRANSCRIPTIONAL ACTIVATION OF THE INTERCELLULAR-ADHESION MOLECULE-1 (CD54) GENE BY HUMAN-T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II TAX IS MEDIATED THROUGH A PALINDROMIC RESPONSE ELEMENT

In vitro infection of T cells with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) resulted in constitutive expression of ICA M-1. Higher levels of ICAM-1 mRNA were expressed in HTLV-transformed c ell lines (MT-2, MoT, C8166) when compared with uninfected T cell line s (A301), We demonstrate that this activation is conferred through a s ite on the ICAM-1 promoter that is activated in trans by the Tax prote in of HTLV-I and HTLV-II. Enhanced promoter activity was detected when the ICAM-1 construct (-1162/+1) was transfected into HTLV-I-infected (MT-2), HTLV-II-infected (MoT, AI 1050), or an HTLV-I Tax-only-express ing (C8166) cell line as compared to the uninfected T cell line (A3.01 ). Cotransfection of the uninfected T cell line A3.01 with the ICAM co nstruct along with Tax-I and Tax-II expression plasmid also resulted i n increased promoter activity, Furthermore, experiments with deletion constructs of the ICAM-1 promoter region indicated that a region betwe en -88 and -53 bp relative to the transcription start site is sufficie nt for Tax-inducible CAT expression, This segment includes an Il-bp pa lindromic segment (TTTCCGGGAAA) that has homology with the IFN-gamma a nd IL-6 response element, An Il-bp segment containing this regulatory region proved to be sufficient to confer Tax-I and Tax-II inducibility on a heterologous promoter (TK-CAT), Taken together these findings in dicate that constitutive expression of ICAM-1 by HTLV-infected cells i s influenced by the viral trans-activator protein Tax, This increased expression of ICAM-1 in response to the Tax protein may play an import ant role in the lymphoproliferation associated with HTLV infection.