title: Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription.
abstract: Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160-250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection.
authors.affiliation: 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
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kusano
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Eizuru
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus