TY  - JOUR
A1  - Koppers-Lalic, Danijela
A1  - Verweij, Marieke C.
A1  - Lipinska, Andrea D.
A1  - Wang, Ying
A1  - Quinten, Edwin
A1  - Reits, Eric A.
A1  - Koch, Joachim
A1  - Loch, Sandra
A1  - Marcondes Rezende, Marisa
A1  - Daus, Franz
A1  - Bienkowska-Szewczyk, Krystyna
A1  - Osterrieder, Nikolaus
A1  - Mettenleiter, Thomas C.
A1  - Heemskerk, Mirjam H. M.
A1  - Tampé, Robert
A1  - Neefjes, Jacques J.
A1  - Chowdhury, Shafiqul I.
A1  - Ressing, Maaike E.
A1  - Rijsewijk, Frans A. M.
A1  - Wiertz, Emmanuel J. H. J.
T1  - Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP
T2  - PLoS pathogens
N2  - 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.
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/5842
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-57824
SN  - 1553-7374
N1  - © 2008 Koppers-Lalic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 4
IS  - (5): e1000080
SP  - 1
EP  - 14
PB  - PLoS
CY  - Lawrence, Kan.
ER  -