Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein.
Like other pathogenic viruses, HIV-1 down-modulates surface expression of major histocompatibility complex class I (MHC-I) molecules in infected cells, thus impairing lysis by cytotoxic T lymphocytes. We have observed that this phenomenon depends on the expression of Nef. nef is an early gene of primate lentiviruses, which is necessary for maintaining high virus loads and inducing AIDS. Nef is not necessary for viral replication in vitro and stimulates the endocytosis of CD4. We show that the expression of MHC-I at the surface of lymphoid, monocytic and epithelial cells was reduced in the presence of Nef protein from various HIV-1 strains. Whereas MHC-I protein synthesis and transport through the endoplasmic reticulum and cis Golgi apparatus occurred normally in Nef(+) cells, surface MHC-I molecules were rapidly internalized, accumulated in endosomal vesicles and were degraded. The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response.
Schwartz
O
O
Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France.
Maréchal
V
V
Le Gall
S
S
Lemonnier
F
F
Heard
J M
JM
D002460:Cell Line; D015536:Down-Regulation; D004705:Endocytosis / Q000276:immunology*; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015754:Genes, nef; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus