The Pleiotropic Effects of YBX1 on HTLV-1 Transcription

Abstract

HTLV-1 is an oncogenic human retrovirus and the etiologic agent of the highly aggressive ATL malignancy. Two viral genes, Tax and Hbz, are individually linked to oncogenic transformation and play an important role in the pathogenic process. Consequently, regulation of HTLV-1 gene expression is a central feature in the viral lifecycle and directly contributes to its pathogenic potential. Herein, we identified the cellular transcription factor YBX1 as a binding partner for HBZ. We found YBX1 activated transcription and enhanced Tax-mediated transcription from the viral 5′ LTR promoter. Interestingly, YBX1 also interacted with Tax. shRNA-mediated loss of YBX1 decreased transcript and protein abundance of both Tax and HBZ in HTLV-1-transformed T-cell lines, as well as Tax association with the 5′ LTR. Conversely, YBX1 transcriptional activation of the 5′ LTR promoter was increased in the absence of HBZ. YBX1 was found to be associated with both the 5′ and 3′ LTRs in HTLV-1-transformed and ATL-derived T-cell lines. Together, these data suggest that YBX1 positively influences transcription from both the 5′ and 3′ promoter elements. YBX1 is able to interact with Tax and help recruit Tax to the 5′ LTR. However, through interactions with HBZ, YBX1 transcriptional activation of the 5′ LTR is repressed.