Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation.
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 IFNgamma and TNFalpha, 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.
Hammarlund
Erika
E
Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.
Dasgupta
Anindya
A
Pinilla
Clemencia
C
Norori
Patricia
P
Früh
Klaus
K
Slifka
Mark K
MK
D017951:Antigen Presentation / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D045908:Mpox, Monkeypox / Q000276:immunology*; D008993:Monkeypox virus / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014779:Virus Replication
D017252:CD3 Complex
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