title: The human immunodeficiency virus (HIV) Rev-binding protein (HRB) is a co-factor for HIV-1 Nef-mediated CD4 downregulation.
abstract: Human immunodeficiency virus type 1 (HIV-1)-mediated CD4 downregulation is an important determinant of viral replication in vivo. Research on cellular co-factors involved in this process could lead to the identification of potential therapeutic targets. We found that CD4 surface levels were significantly higher in HIV-1-infected cells knocked-down for the HIV Rev-binding protein (HRB) compared with control cells. HRB knock-down affected CD4 downregulation induced by Nef but not by HIV-1 Vpu. Interestingly, the knock-down of the related protein HRBL (HRB-like), but not of the HRB interaction partner EPS15 (epidermal growth factor receptor pathway substrate 15), increased CD4 levels in Vpu-expressing cells significantly. Both of these proteins are known to be involved in HIV-1-mediated CD4 downregulation as co-factors of HIV-1 Nef. These results identify HRB as a previously unknown co-factor for HIV-1 Nef-mediated CD4 downregulation and highlight differences with the related protein HRBL, which affects the CD4 downregulation in a dual role as co-factor of both HIV-1 Nef and Vpu.
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Alessia
authors.initials: A
authors.lastname: Landi
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Cristina Garcia
authors.initials: CG
authors.lastname: Timermans
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Naessens
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanderstraeten
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
mesh_terms: D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D015704:CD4 Antigens; D054298:Human Immunodeficiency Virus Proteins; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; C119724:AGFG1 protein, human; C514860:rev protein, Human Immunodeficiency Virus-1; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins