title: XBP-1, a novel human T-lymphotropic virus type 1 (HTLV-1) tax binding protein, activates HTLV-1 basal and tax-activated transcription.
abstract: X-box binding protein 1 (XBP-1), a basic leucine zipper transcription factor, plays a key role in the cellular unfolded protein response (UPR). There are two XBP-1 isoforms in cells, spliced XBP-1S and unspliced XBP-1U. XBP-1U has been shown to bind to the 21-bp Tax-responsive element of the human T-lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR) in vitro and transactivate HTLV-1 transcription. Here we identify XBP-1S as a transcription activator of HTLV-1. Compared to XBP-1U, XBP-1S demonstrates stronger activating effects on both basal and Tax-activated HTLV-1 transcription in cells. Our results show that both XBP-1S and XBP-1U interact with Tax and bind to the HTLV-1 LTR in vivo. In addition, elevated mRNA levels of the gene for XBP-1 and several UPR genes were detected in the HTLV-1-infected C10/MJ and MT2 T-cell lines, suggesting that HTLV-1 infection may trigger the UPR in host cells. We also identify Tax as a positive regulator of the expression of the gene for XBP-1. Activation of the UPR by tunicamycin showed no effect on the HTLV-1 LTR, suggesting that HTLV-1 transcription is specifically regulated by XBP-1. Collectively, our study demonstrates a novel host-virus interaction between a cellular factor XBP-1 and transcriptional regulation of HTLV-1.
authors.affiliation: Expression Engineering Group, Bioprocessing Technology Institute, 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore. jimmy_chao@bti.a-star.edu.sg
authors.forename: Sebastian C Y
authors.initials: SC
authors.lastname: Ku
authors.forename: Jialing
authors.initials: J
authors.lastname: Lee
authors.forename: Joanne
authors.initials: J
authors.lastname: Lau
authors.forename: Meera
authors.initials: M
authors.lastname: Gurumurthy
authors.forename: Raymond
authors.initials: R
authors.lastname: Ng
authors.forename: Siew Hui
authors.initials: SH
authors.lastname: Lwa
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: Zachary
authors.initials: Z
authors.lastname: Klase
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
authors.forename: Sheng-Hao
authors.initials: SH
authors.lastname: Chao
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D015490:HTLV-I Infections / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012367:RNA, Viral / Q000032:analysis; D000071701:Regulatory Factor X Transcription Factors; D020079:Terminal Repeat Sequences; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D009687:Nuclear Proteins; D012367:RNA, Viral; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1