Journal of Biological Chemistry · 2005 · 63 citations · 39 references
Life SciencesImmunologyMolecular BiologyIntracellular TransportMembrane TraffickingMolecular VirologyAdaptor Protein ComplexesAntigen Presentation RegulationEndomembrane SystemIntracellular TraffickingSecretory PathwayViral EntryAdaptor Protein Complex 1Antigen Presentation In Viral InfectionMajor Histocompatibility Complex Class I PresentationMhc Class I MoleculesMhc Class I TraffickingTrans-golgi TransportViral Evasion MechanismsViral Immune Evasion Mechanisms
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.
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