The short cytoplasmic tail of HLA-G determines its resistance to HIV-1 Nef-mediated cell surface downregulation.
During infection with the human immunodeficiency virus type 1 (HIV-1), selective downregulation of major histocompatibility complex (MHC) class I molecules by Nef protein allows infected cells to be protected from natural killer (NK) cell lysis and to escape the HIV-specific cytotoxic T-lymphocyte response. The nonclassical MHC class I molecule human leukocyte antigen (HLA)-G is mainly expressed in placental tissues and in thymic epithelial cells. Using chimeric molecules and flow cytometry, we show that in contrast with HLA-A2, the non classical MHC class I molecule HLA-G is resistant to Nef-induced cell surface downregulation solely because of the length of its intracytoplasmic domain. Moreover, confocal microscopy analysis indicates that Nef does not delocalize HLA-G molecules from the cell surface, whereas HLA-G molecules extended with the cytoplasmic tail of HLA-A2 accumulate intracellularly with Nef. Together, these data demonstrate that the short cytoplasmic tail of HLA-G confers resistance to Nef-induced downregulation and intracellular accumulation. This resistance may have functional consequences during the course of HIV infection.
Pizzato
Nathalie
N
Centre de Physiopathologie Toulouse-Purpan, INSERM U563, Hôpital Purpan, Toulouse, France.
Derrien
Muriel
M
Lenfant
Françoise
F
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D006680:HLA Antigens; D015234:HLA-A Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus