title: Human immunodeficiency virus Nef induces rapid internalization of the T-cell coreceptor CD8alphabeta.
abstract: Human immunodeficiency virus (HIV) Nef is a membrane-associated protein decreasing surface expression of CD4, CD28, and major histocompatibility complex class I on infected cells. We report that Nef strongly down-modulates surface expression of the beta-chain of the CD8alphabeta receptor by accelerated endocytosis, while CD8 alpha-chain expression is less affected. By mutational analysis of the cytoplasmic tail of the CD8 beta-chain, an FMK amino acid motif was shown to be critical for Nef-induced endocytosis. Although independent of CD4, endocytosis of the CD8 beta-chain was abrogated by the same mutations in Nef that affect CD4 down-regulation, suggesting common molecular interactions. The ability to down-regulate the human CD8 beta-chain was conserved in HIV-1, HIV-2, and simian immunodeficiency virus SIVmac239 Nef and required an intact AP-2 complex. The Nef-mediated internalization of receptors, such as CD4, major histocompatibility complex class I, CD28, and CD8alphabeta, may contribute to the subversion of the host immune system and progression towards AIDS.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospita, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.forename: Inge
authors.initials: I
authors.lastname: Van de Walle
authors.forename: Evelien
authors.initials: E
authors.lastname: Naessens
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Coene
authors.forename: Christophe
authors.initials: C
authors.lastname: Stove
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D016827:CD8 Antigens; C067361:CD8 receptor; D011948:Receptors, Antigen, T-Cell; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human