1. HIV-1 Nef disrupts antigen presentation early in the secretory pathway.
- Author
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Kasper MR, Roeth JF, Williams M, Filzen TM, Fleis RI, and Collins KL
- Subjects
- Adenoviridae metabolism, Amino Acid Sequence, Biological Transport, Cell Membrane metabolism, Cell Separation, Cytoplasm metabolism, Flow Cytometry, Gene Products, nef chemistry, Genes, MHC Class I, Golgi Apparatus metabolism, HLA-A2 Antigen chemistry, HeLa Cells, Humans, Immunoprecipitation, Lysosomes metabolism, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Phosphates chemistry, Phosphorylation, Protein Binding, RNA Interference, Sequence Homology, Amino Acid, T-Lymphocytes metabolism, Temperature, Time Factors, trans-Golgi Network, Antigen Presentation, Gene Products, nef physiology
- Abstract
Human immunodeficiency virus, type 1 Nef disrupts viral antigen presentation and promotes viral immune evasion from cytotoxic T lymphocytes. There is evidence that Nef acts early in the secretory pathway to redirect major histocompatibility complex class I (MHC-I) from the trans-Golgi network to the endolysosomal pathway. However, a competing model suggests that Nef acts much later by accelerating MHC-I turnover at the cell surface. Here we demonstrate that Nef targets early forms of MHC-I molecules in the endoplasmic reticulum by preferentially binding hypophosphorylated cytoplasmic tails. The Nef-MHC-I complex migrates normally into the Golgi apparatus but subsequently fails to arrive at the cell surface and become phosphorylated. Cell type-specific differences in the rate of MHC-I transport through the secretory pathway correlate with responsiveness to Nef and co-precipitation of adaptor protein 1 with the Nef.MHC-I complex. We propose that the assembly of a Nef.MHC-I.adaptor protein 1 complex early in the secretory pathway is important for Nef activity.
- Published
- 2005
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