TY  - JOUR
A1  - Lin, Jiacheng
A1  - Eggensperger, Sabine
A1  - Hank, Susanne
A1  - Wycisk, Agnes Isabella
A1  - Wieneke, Ralph
A1  - Mayerhofer, Peter Uli
A1  - Tampé, Robert
T1  - A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome
T2  - PLoS pathogens
N2  - Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/36383
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-363830
SN  - 1553-7374
SN  - 1553-7366
N1  - Copyright: © 2014 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 10
IS  - (12):e1004554
PB  - PLoS
CY  - Lawrence, Kan.
ER  -