Human phospholipid scramblase 1 interacts with and regulates transactivation of HTLV-1 Tax.
Human phospholipid scramblase (PLSCR) 1 expression is strongly activated in response to interferon (IFN) treatment and viral infection, and PLSCR1 is necessary for the IFN-dependent induction of gene expression and antiviral activity. We show here that PLSCR1 directly interacts with human T-cell leukemia virus type-1 (HTLV-1) Tax in vitro and in vivo. This interaction reduced the cytoplasmic distribution of Tax. PLSCR1 efficiently repressed the Tax-mediated transactivation of the HTLV-1 long terminal repeat and the NF-κB binding site reporter constructs in an interaction-dependent manner in COS-1 and Tax-producing HTLV-1-infected T cell lines. Furthermore, we show that PLSCR1 repressed the homodimerization of Tax in vitro. These data reveal for the first time that PLSCR1 specifically interacts with HTLV-1 Tax and negatively regulates its transactivation activity by altering the subcellular distribution and the homodimerization of Tax. PLSCR1 may play an important role in the IFN-mediated repression of Tax-dependent transactivation during HTLV-1 infection.
Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. skusano@m2.kufm.kagoshima-u.ac.jp
Shuichi
S
Kusano
Yoshito
Y
Eizuru
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization / Q000187:drug effects; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects*
D016356:Gene Products, tax; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; C514970:tax protein, Human T-lymphotrophic virus 1