Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.

Herpesviruses are large DNA viruses that are highly abundant within their host populations. Even in the presence of a healthy immune system, these viruses manage to cause lifelong infections. This persistence is partially mediated by the virus entering latency, a phase of infection characterized by...

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Main Authors: Marieke C Verweij, Daniëlle Horst, Bryan D Griffin, Rutger D Luteijn, Andrew J Davison, Maaike E Ressing, Emmanuel J H J Wiertz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-04-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1004743
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author Marieke C Verweij
Daniëlle Horst
Bryan D Griffin
Rutger D Luteijn
Andrew J Davison
Maaike E Ressing
Emmanuel J H J Wiertz
author_facet Marieke C Verweij
Daniëlle Horst
Bryan D Griffin
Rutger D Luteijn
Andrew J Davison
Maaike E Ressing
Emmanuel J H J Wiertz
author_sort Marieke C Verweij
collection DOAJ
description Herpesviruses are large DNA viruses that are highly abundant within their host populations. Even in the presence of a healthy immune system, these viruses manage to cause lifelong infections. This persistence is partially mediated by the virus entering latency, a phase of infection characterized by limited viral protein expression. Moreover, herpesviruses have devoted a significant part of their coding capacity to immune evasion strategies. It is believed that the close coexistence of herpesviruses and their hosts has resulted in the evolution of viral proteins that specifically attack multiple arms of the host immune system. Cytotoxic T lymphocytes (CTLs) play an important role in antiviral immunity. CTLs recognize their target through viral peptides presented in the context of MHC molecules at the cell surface. Every herpesvirus studied to date encodes multiple immune evasion molecules that effectively interfere with specific steps of the MHC class I antigen presentation pathway. The transporter associated with antigen processing (TAP) plays a key role in the loading of viral peptides onto MHC class I molecules. This is reflected by the numerous ways herpesviruses have developed to block TAP function. In this review, we describe the characteristics and mechanisms of action of all known virus-encoded TAP inhibitors. Orthologs of these proteins encoded by related viruses are identified, and the conservation of TAP inhibition is discussed. A phylogenetic analysis of members of the family Herpesviridae is included to study the origin of these molecules. In addition, we discuss the characteristics of the first TAP inhibitor identified outside the herpesvirus family, namely, in cowpox virus. The strategies of TAP inhibition employed by viruses are very distinct and are likely to have been acquired independently during evolution. These findings and the recent discovery of a non-herpesvirus TAP inhibitor represent a striking example of functional convergent evolution.
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spelling doaj-art-53438da65fdd4d49ba4bffa4d8db32932025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-04-01114e100474310.1371/journal.ppat.1004743Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.Marieke C VerweijDaniëlle HorstBryan D GriffinRutger D LuteijnAndrew J DavisonMaaike E RessingEmmanuel J H J WiertzHerpesviruses are large DNA viruses that are highly abundant within their host populations. Even in the presence of a healthy immune system, these viruses manage to cause lifelong infections. This persistence is partially mediated by the virus entering latency, a phase of infection characterized by limited viral protein expression. Moreover, herpesviruses have devoted a significant part of their coding capacity to immune evasion strategies. It is believed that the close coexistence of herpesviruses and their hosts has resulted in the evolution of viral proteins that specifically attack multiple arms of the host immune system. Cytotoxic T lymphocytes (CTLs) play an important role in antiviral immunity. CTLs recognize their target through viral peptides presented in the context of MHC molecules at the cell surface. Every herpesvirus studied to date encodes multiple immune evasion molecules that effectively interfere with specific steps of the MHC class I antigen presentation pathway. The transporter associated with antigen processing (TAP) plays a key role in the loading of viral peptides onto MHC class I molecules. This is reflected by the numerous ways herpesviruses have developed to block TAP function. In this review, we describe the characteristics and mechanisms of action of all known virus-encoded TAP inhibitors. Orthologs of these proteins encoded by related viruses are identified, and the conservation of TAP inhibition is discussed. A phylogenetic analysis of members of the family Herpesviridae is included to study the origin of these molecules. In addition, we discuss the characteristics of the first TAP inhibitor identified outside the herpesvirus family, namely, in cowpox virus. The strategies of TAP inhibition employed by viruses are very distinct and are likely to have been acquired independently during evolution. These findings and the recent discovery of a non-herpesvirus TAP inhibitor represent a striking example of functional convergent evolution.https://doi.org/10.1371/journal.ppat.1004743
spellingShingle Marieke C Verweij
Daniëlle Horst
Bryan D Griffin
Rutger D Luteijn
Andrew J Davison
Maaike E Ressing
Emmanuel J H J Wiertz
Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
PLoS Pathogens
title Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
title_full Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
title_fullStr Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
title_full_unstemmed Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
title_short Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution.
title_sort viral inhibition of the transporter associated with antigen processing tap a striking example of functional convergent evolution
url https://doi.org/10.1371/journal.ppat.1004743
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