Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein

作者：H. Valentin, Isabelle Lemasson, Samir W. Hamaia, Huguette Casse, Stéphane König, Christian Albert Devaux, Louis Gazzolo · 发表于：Journal of Virology · 年份：1997 · DOI：10.1128/jvi.71.11.8522-8530.1997 · 被引用次数：46 · 研究领域：T-cell and Retrovirus Studies、Vector-Borne Animal Diseases

Recruitment and extravasation of T cells through the blood-brain barrier are favored by adhesion molecule-mediated interactions of circulating T cells with endothelial cells. Since a common pathological finding in human T-cell leukemia virus type 1 (HTLV-1)-associated diseases is the infiltration of HTLV-1-infected T lymphocytes into various organs, we have looked for the profile of adhesion molecules expressed by HTLV-1-transformed T cells. Flow cytometry analysis indicated that these cells were expressing high levels of vascular cell adhesion molecule 1 (VCAM-1 [CD106]), a 110-kDa member of the immunoglobulin gene superfamily, first identified on endothelial cells stimulated with inflammatory cytokines. This adhesion molecule was also expressed by T cells obtained from one patient with HTLV-1-associated myelopathy/tropical spastic paraparesis but not by activated T cells isolated from one normal blood donor. The role of the viral trans-activator Tax protein in the induction of VCAM-1 was first indicated by the detection of this adhesion molecule on Jurkat T-cell clones stably expressing the tax gene. The effect of Tax on VCAM-1 gene transcription was next confirmed in JPX-9 cells, a subclone of Jurkat cells, carrying the tax sequences under the control of an inducible promoter. Furthermore, deletion and mutation analyses of the VCAM-1 promoter performed with chloramphenicol acetyltransferase constructs revealed that Tax was trans activating the VCAM-1 promoter via two NF-ka...