Viral Inhibition of the Transporter Associated with Antigen Processing (TAP): A Striking Example of Functional Convergent Evolution

Marieke Verweij, Daniëlle Horst, Bryan D. Griffin, Rutger D. Luteijn, Andrew J. Davison, Maaike E. Ressing, Emmanuel J H J Wiertz

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1004743
JournalPLoS Pathogens
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2015

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Herpesviridae
Viruses
Immune Evasion
Cytotoxic T-Lymphocytes
Viral Proteins
Immune System
Cowpox virus
Virus Latency
Histocompatibility Antigens Class I
Peptides
DNA Viruses
Antigen Presentation
Infection
transporter associated with antigen processing (TAP)
Antiviral Agents
Immunity
Population
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Verweij, M., Horst, D., Griffin, B. D., Luteijn, R. D., Davison, A. J., Ressing, M. E., & 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]. https://doi.org/10.1371/journal.ppat.1004743

Viral Inhibition of the Transporter Associated with Antigen Processing (TAP) : A Striking Example of Functional Convergent Evolution. / Verweij, Marieke; Horst, Daniëlle; Griffin, Bryan D.; Luteijn, Rutger D.; Davison, Andrew J.; Ressing, Maaike E.; Wiertz, Emmanuel J H J.

In: PLoS Pathogens, Vol. 11, No. 4, e1004743, 01.04.2015.

Research output: Contribution to journalArticle

Verweij, M, Horst, D, Griffin, BD, Luteijn, RD, Davison, AJ, Ressing, ME & Wiertz, EJHJ 2015, 'Viral Inhibition of the Transporter Associated with Antigen Processing (TAP): A Striking Example of Functional Convergent Evolution', PLoS Pathogens, vol. 11, no. 4, e1004743. https://doi.org/10.1371/journal.ppat.1004743
Verweij, Marieke ; Horst, Daniëlle ; Griffin, Bryan D. ; Luteijn, Rutger D. ; Davison, Andrew J. ; Ressing, Maaike E. ; Wiertz, Emmanuel J H J. / Viral Inhibition of the Transporter Associated with Antigen Processing (TAP) : A Striking Example of Functional Convergent Evolution. In: PLoS Pathogens. 2015 ; Vol. 11, No. 4.
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