Ebola virus-like particle-induced activation of NF-kappaB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain.
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.
Martinez
Osvaldo
O
Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L Levy Place, New York, NY 10029, USA.
Valmas
Charalampos
C
Basler
Christopher F
CF
D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D029043:Ebolavirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D008854:Microscopy, Electron; D009077:Mucins / Q000737:chemistry / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology / Q000648:ultrastructure
D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D009077:Mucins; D016328:NF-kappa B; D014157:Transcription Factors; D014764:Viral Proteins; D048049:Extracellular Signal-Regulated MAP Kinases