Ebola virus-like particle-induced activation of NF-κB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain

Osvaldo Martinez, Charalampos Valmas, Christopher F. Basler

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Dendritic cells (DCs), important early targets of Ebola virus (EBOV) infection in vivo, are activated by Ebola virus-like particles (VLPs). To better understand this phenomenon, we have systematically assessed the response of DCs to VLPs of different compositions. VLPs containing the viral matrix protein (VP40) and the viral glycoprotein (GP), were found to induce a proinflammatory response highly similar to a prototypical DC activator, LPS. This response included the production of several proinflammatory cytokines, activation of numerous transcription factors including NF-kappaB, the functional importance of which was demonstrated by employing inhibitors of NF-kappaB activation, and activation of ERK1/2 MAP kinase. In contrast, VLPs constituted with a mutant GP lacking the heavily glycosylated mucin domain showed impaired NF-kappaB and Erk activation and induced less DC cytokine production. We conclude that the GP mucin domain is required for VLPs to stimulate human dendritic cells through NF-kappaB and MAPK signaling pathways.

Original languageEnglish
Pages (from-to)342-354
Number of pages13
JournalVirology
Volume364
Issue number2
DOIs
StatePublished - 1 Aug 2007

Keywords

  • Cytokine
  • Dendritic cell
  • Ebola virus
  • Erk
  • Filovirus
  • Inhibitor
  • MAP kinase
  • NF-kB
  • Proinflammatory
  • Signaling
  • Transcription factor

Fingerprint

Dive into the research topics of 'Ebola virus-like particle-induced activation of NF-κB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain'. Together they form a unique fingerprint.

Cite this