Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation

Erika Hammarlund, Anindya Dasgupta, Clemencia Pinilla, Patricia Norori, Klaus Früh, Mark K. Slifka

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Monkeypox virus (MPV) is a virulent human pathogen that has gained increased attention because of its potential use as a bioterrorism agent and inadvertent introduction into North America in 2003. The US outbreak also provided an important opportunity to study MPV-specific T cell immunity. Although MPV-specific CD4+ and CD8+ T cells could recognize vaccinia virus (VV)-infected monocytes and produce inflammatory cytokines such as IFNγ and TNFα, they were largely incapable of responding to autologous MPV-infected cells. Further analysis revealed that, unlike cowpox virus (CPV), MPV did not interfere with MHC expression or intracellular transport of MHC molecules. Instead, MPV-infected cells were capable of preventing T cell receptor (TcR)-mediated T cell activation in trans. The ability to trigger a state of nonresponsiveness represents a unique MHC-independent mechanism for blocking antiviral T cell activation and inflammatory cytokine production and is likely an important attribute involved with viral dissemination in the infected host.

Original languageEnglish (US)
Pages (from-to)14567-14572
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number38
DOIs
StatePublished - Sep 23 2008

Keywords

  • Immune evasion
  • Orthopoxvirus
  • T cell immunity

ASJC Scopus subject areas

  • General

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