HIV-1 down-regulates the expression of CD1d via Nef.
HIV-1 has evolved several strategies to subvert host immune responses to the infected cells. One is to inhibit CTL recognition by HIV-1 Nef-mediated down-regulation of MHC-I expression on the surface of infected cells. Here we report that Nef also reduces the expression of the non-classical MHC-I like CD1d molecule, a third lineage of antigen-presenting molecule, which presents lipid antigens. Nef achieves this by increasing internalization of CD1d molecules from the cell surface and retaining CD1d in the trans-Golgi-network (TGN). This effect depends on a tyrosine-based motif present in CD1 cytoplasmic tail as well as the actions of four Nef motifs, which are known to be involved in the down-regulation of MHC-I or CD4. These results suggest that Nef regulates intracellular trafficking of CD1d via a distinct but shared pathway with MHC-I and CD4. Thus, HIV-1 reduces the visibility of its infected cells not only to MHC-I-restricted T cells but also to CD1d-restricted NKT cells. Given that CD1d-restricted T cells have unique effector and regulatory functions in innate and adapted immune responses as compared with their counterpart MHC-restricted T cells, our data provide additional new insights into molecular basis of HIV-1-mediated damage to the immune system.
Chen
Nan
N
MRC Human Immunology Unit and Molecular Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK.
McCarthy
Corinna
C
Drakesmith
Hal
H
Li
Demin
D
Cerundolo
Vincenzo
V
McMichael
Andrew J
AJ
Screaton
Gavin R
GR
Xu
Xiao-Ning
XN
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000276:immunology; D055610:Antigens, CD1d; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology*; D006056:Golgi Apparatus / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus