Short Communication HTLV Type I Tax Activation of the CXCR4 Promoter by Association with Nuclear Respiratory Factor 1

Abstract

Human T lymphotropic virus type I trans-activator Tax protein regulates expression of several cellular genes that are involved in cellular activation, proliferation, and transformation. Tax mediates its regulatory activity through interaction with cellular transcription factors such as members of the cAMP-responsive elementbinding factors/ATF family or the NF-kappa B/Rel family. In this study we have demonstrated that Tax trans -activates the promoter for CXCR4, a coreceptor for T cell-tropic HIV-1 through its association with nuclear respiratory factor 1 (NRF1). The promoter region for CXCR4 contains an NRF1-binding site, which is crucial for basal and Tax-induced activity. Glutathione S-transferase (GST) pull-down experiments showed association of GST-Tax fusion protein with NRF1 in vitro. Expression of Tax, in addition to stimulation with phorbol myristate acetate and ionomycin, increased formation of the NRF1 complex in a gel-mobility shift assay, indicating that Tax association with NRF1 in vivo facilitates its DNA binding. HTLV-I Tax activation of CXCR4 may contribute to the rapid progression of HIV disease observed in certain coinfected individuals.