Varicellovirus UL49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP
| Autor: | Jacques Neefjes, Danijela Koppers-Lalic, Frans A.M. Rijsewijk, Joachim Koch, Mirjam H.M. Heemskerk, Krystyna Bieńkowska-Szewczyk, Nikolaus Osterrieder, Ying Wang, Franz Daus, Edwin Quinten, Marisa Marcondes Rezende, Robert Tampé, Maaike E. Ressing, Thomas C. Mettenleiter, Eric Reits, Sandra Loch, Shafiqul I. Chowdhury, Andrea D. Lipińska, Marieke C. Verweij, Emmanuel J. H. J. Wiertz |
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| Přispěvatelé: | Amsterdam Gastroenterology Endocrinology Metabolism, Cell Biology and Histology |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Swine
animal diseases viruses Immunology/Immunomodulation Viral Envelope Proteins Transduction Genetic Cytotoxic T cell Varicellovirus lcsh:QH301-705.5 cytomegalovirus us6 glycoprotein Recombination Genetic Antigen Presentation Milieubeleid Transporter associated with antigen processing Herpesvirus 1 Suid major histocompatibility complex Environmental Policy Protein Transport Immunology/Antigen Processing and Recognition viral immune evasion CVI - Division Virology Research Article Herpesvirus 1 Equid lcsh:Immunologic diseases. Allergy ID - Infectieziekten Cell Survival Immunology Antigen presentation Biology Virology/Immune Evasion Major histocompatibility complex Microbiology equine herpesvirus-1 Dogs CVI - Divisie Virologie down-regulation ddc:570 Virology Cell Line Tumor MHC class I Genetics Animals Humans mhc class-i Horses ligase mk3 Molecular Biology Herpesvirus 1 Bovine finger protein MHC class I antigen molecular-mechanism MHC Class I Gene lcsh:Biology (General) Peptide transport biology.protein Parasitology ATP-Binding Cassette Transporters Cattle lcsh:RC581-607 peptide-loading complex |
| Zdroj: | PLoS Pathogens, Vol 4, Iss 5, p e1000080 (2008) PLoS Pathogens 4 (2008) 5 PLoS Pathogens, 4(5) PLoS Pathogens PLoS pathogens, 4(5). Public Library of Science |
| ISSN: | 1553-7366 |
| DOI: | 10.1371/journal.ppat.1000080 |
| Popis: | Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms. Author Summary Herpesviruses have the conspicuous property that they persist for life in the infected host. This is also the case for varicelloviruses, a large subfamily of herpesviruses with representatives in humans (varicella zoster virus or VZV), cattle (bovine herpesvirus 1 or BHV-1), pigs (pseudorabies virus or PRV), and horses (equine herpesvirus or EHV type 1 and 4), among many others. Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in this process, as TAP imports peptides into the compartment where peptide loading of the MHC class I molecules takes place. In this study, we show that the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 all block the supply of peptides through the inhibition of TAP, but that the mechanisms employed by these proteins to inhibit TAP function exhibit surprising diversity. VZV UL49.5, on the other hand, binds to TAP, but does not interfere with peptide transport. Our study classifies the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms. |
| Databáze: | OpenAIRE |
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