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.