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Article
Nature Medicine  2, 338 - 342 (1996)
doi:10.1038/nm0396-338

Endocytosis of major histocompatibility complex class I molecules is induced by the HIV−1 Nef protein

Olivier Schwartz1, 3, Valerie Maréchal1, Sylvie Le Gall1, François Lemonnier2 & Jean-Michel Heard1

  1Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157

  2Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France

  3Correspondence should be addressed to O.S.

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 lymphocytes1,2. We have observed that this phenomenon depends on the expression of Nef. nef is an early gene of primate lentiviruses3, which is necessary for maintaining high virus loads and inducing AIDS (ref. 4). Nef is not necessary for viral replication in vitro and stimulates the endocytosis of CD4 (ref. 5−8). 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.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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