Corking the bottleneck: the transporter associated with antigen processing as a target for immune subversion by viruses.
In this chapter, mechanisms are reviewed that viruses use to inhibit the function of the peptide transporter associated with antigen processing (TAP), which translocates cytosolic peptides into the endoplasmic reticulum (ER) for binding to MHC class I molecules. Although some DNA viruses, such as adenovirus or EBV, downmodulate TAP expression on the transcriptional level, members of the alpha and beta subfamily of herpesviruses, such as herpes simplex virus (HSV) and human cytomegalovirus (HCMV), express proteins that bind to TAP and interfere with peptide translocation. The modes of action of the HSV-encoded cytosolic TAP inhibitor ICP47 and the HCMV-encoded ER-resident TAP inhibitor gpUS6 are discussed in detail. Viral interference with antigen presentation through TAP inhibition is not only relevant for the immunobiology of persistent viral infections but also contributes to the understanding of the translocation mechanism utilized by the ATP-binding cassette transporter TAP.
Momburg
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Deutsches Krebsforschungszentrum, Department of Molecular Immunology, 69120 Heidelberg, Germany.
Hengel
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D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D017951:Antigen Presentation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D016601:RNA-Binding Proteins / Q000378:metabolism; D018139:Simplexvirus / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; C432877:US6 protein, Human cytomegalovirus; D014764:Viral Proteins