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

Verweij, M. C., Horst, D., Griffin, B. D., Luteijn, R. D., Davison, A. J. , Ressing, M. E. and Wiertz, E. J.H.J. (2015) Viral inhibition of the transporter associated with antigen processing (TAP): a striking example of functional convergent evolution. PLoS Pathogens, 11(4), e1004743. (doi: 10.1371/journal.ppat.1004743) (PMID:25880312) (PMCID:PMC4399834)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davison, Professor Andrew
Authors: Verweij, M. C., Horst, D., Griffin, B. D., Luteijn, R. D., Davison, A. J., Ressing, M. E., and Wiertz, E. J.H.J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in PLoS Pathogens 11(4):e1004743
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH