Human immunodeficiency virus Nef induces rapid internalization of the T-cell coreceptor CD8alphabeta.
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.
Stove
Veronique
V
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospita, Belgium.
Van de Walle
Inge
I
Naessens
Evelien
E
Coene
Elisabeth
E
Stove
Christophe
C
Plum
Jean
J
Verhasselt
Bruno
B
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
D016827:CD8 Antigens; C067361:CD8 receptor; D011948:Receptors, Antigen, T-Cell; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human