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

@article{Schwartz1996EndocytosisOM,
  title={Endocytosis of major histocompatibility complex class I molecules is induced by the HIV–1 Nef protein},
  author={Olivier Schwartz and Valérie Maréchal and Sylvie Le Gall and François Lemonnier and Jean Michel Heard},
  journal={Nature Medicine},
  year={1996},
  volume={2},
  pages={338-342}
}
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… 

HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway.

It is shown here that endocytosis is not required for Nef-mediated downmodulation of MHC-I molecules, and it is proposed that Nef diverts M HC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface.

HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes

These results support a model in which Nef relocalizes MHC-I by acting as a connector between M HC-I’s cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.

HIV-1 Nef impairs MHC class II antigen presentation and surface expression

It is shown that HIV-1 Nef inhibits MHC II restricted peptide presentation to specific T cells and thus may affect the induction of antiviral immune responses and Cooperation between those mechanisms may enable Nef to efficiently inhibit M HC II function.

Transcription of Preintegrated HIV-1 cDNA Modulates Cell Surface Expression of Major Histocompatibility Complex Class I via Nef

The capacity of HIV-1 to modulate MHC-I is not linked to its ability to integrate, and Nef-mediated evasion of host immune responsiveness might be attributable, in part at least, to transcription from unintegrated viral DNA.

HIV-1 Nef Disrupts Antigen Presentation Early in the Secretory Pathway*

It is proposed that the assembly of a Nef·MHC-I·adaptor protein 1 complex early in the secretory pathway is important for Nef activity.

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

Evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV.

Human immunodeficiency virus-1 Nef expression induces intracellular accumulation of multivesicular bodies and major histocompatibility complex class II complexes: potential role of phosphatidylinositol 3-kinase.

It is shown that Nef modifies major histocompatibility complex class II (MHC II) intracellular trafficking and thereby its function, and induces an increase of the number of MVBs where MHC II complexes accumulate.

HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

The importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses, is demonstrated.

The Role of the Nef Protein in MHC-I Downregulation and Viral Immune Evasion by HIV-1

This review will examine how the multifunctional Nef protein can mediate downregulation of the Major Histocompatibility Complex (MHC) I proteins from the surface of infected cells as a means of immune evasion by HIV.

HIV-1 Nef Promotes Endocytosis of Cell Surface MHC Class II Molecules via a Constitutive Pathway1

HIV-1 Nef-mediated endocytosis of MHCII provides a novel perspective on the regulation of normal MHC II trafficking as well as mechanisms involved in normal M HCII recycling and turnover to mediate the delivery of cell surface MHCii to a lysosomal destination.
...

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