Ebolavirus VP35 suppresses IFN production from conventional but not plasmacytoid dendritic cells

Lawrence W. Leung, Man Seong Park, Osvaldo Martinez, Charalampos Valmas, Carolina B. López, Christopher F. Basler

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Ebolaviruses naturally infect a wide variety of cells including macrophages and dendritic cells (DCs), and the resulting cytokine and interferon-α/ β (IFN) responses of infected cells are thought to influence viral pathogenesis. The VP35 protein impairs RIG-I-like receptor-dependent signaling to inhibit IFN production, and this function has been suggested to promote the ineffective host immune response characteristic of ebolavirus infection. To assess the impact of VP35 on innate immunity in biologically relevant primary cells, we used a recombinant Newcastle disease virus encoding VP35 (NDV/VP35) to infect macrophages and conventional DCs, which primarily respond to RNA virus infection via RIG-I-like pathways. VP35 suppressed not only IFN but also tumor necrosis factor (TNF)-α secretion, which are normally produced from these cells upon NDV infection. Additionally, in cells susceptible to the activity of VP35, IRF7 activation is impaired. In contrast, NDV/VP35 infection of plasmacytoid DCs, which activate IRF7 and produce IFN through TLR-dependent signaling, leads to robust IFN production. When plasmacytoid DCs deficient for TLR signaling were infected, NDV/VP35 was able to inhibit IFN production. Consistent with this, VP35 was less able to inhibit TLR-dependent versus RIG-I-dependent signaling in vitro. These data demonstrate that ebolavirus VP35 suppresses both IFN and cytokine production in multiple primary human cell types. However, cells that utilize the TLR pathway can circumvent this inhibition, suggesting that the presence of multiple viral sensors enables the host to overcome viral immune evasion mechanisms.

Original languageEnglish
Pages (from-to)792-802
Number of pages11
JournalImmunology and Cell Biology
Volume89
Issue number7
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • IRF7
  • dendritic cell
  • ebolavirus
  • interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Leung, L. W., Park, M. S., Martinez, O., Valmas, C., López, C. B., & Basler, C. F. (2011). Ebolavirus VP35 suppresses IFN production from conventional but not plasmacytoid dendritic cells. Immunology and Cell Biology, 89(7), 792-802. https://doi.org/10.1038/icb.2010.169