PMID- 17434557 OWN - NLM STAT- MEDLINE DCOM- 20070801 LR - 20181113 IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 364 IP - 2 DP - 2007 Aug 1 TI - Ebola virus-like particle-induced activation of NF-kappaB and Erk signaling in human dendritic cells requires the glycoprotein mucin domain. PG - 342-54 AB - 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. FAU - Martinez, Osvaldo AU - Martinez O AD - Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L Levy Place, New York, NY 10029, USA. FAU - Valmas, Charalampos AU - Valmas C FAU - Basler, Christopher F AU - Basler CF LA - eng GR - U19 AI062623/AI/NIAID NIH HHS/United States GR - U19 AI062623-030002/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070416 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Cytokines) RN - 0 (IL6 protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Mucins) RN - 0 (NF-kappa B) RN - 0 (Transcription Factors) RN - 0 (Viral Proteins) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Cell Line MH - Cells, Cultured MH - Cytokines/biosynthesis MH - Dendritic Cells/immunology/*metabolism/*virology MH - Ebolavirus/genetics/*pathogenicity/physiology/ultrastructure MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Humans MH - Inflammation Mediators/metabolism MH - Interleukin-6/biosynthesis MH - MAP Kinase Signaling System MH - Microscopy, Electron MH - Mucins/chemistry/genetics MH - NF-kappa B/*metabolism MH - Protein Structure, Tertiary MH - Transcription Factors/metabolism MH - Transfection MH - Viral Proteins/chemistry/genetics/*physiology MH - Virion/genetics/pathogenicity/physiology/ultrastructure PMC - PMC2034500 MID - NIHMS25784 EDAT- 2007/04/17 09:00 MHDA- 2007/08/02 09:00 PMCR- 2008/08/01 CRDT- 2007/04/17 09:00 PHST- 2006/11/22 00:00 [received] PHST- 2007/01/05 00:00 [revised] PHST- 2007/03/09 00:00 [accepted] PHST- 2007/04/17 09:00 [pubmed] PHST- 2007/08/02 09:00 [medline] PHST- 2007/04/17 09:00 [entrez] PHST- 2008/08/01 00:00 [pmc-release] AID - S0042-6822(07)00178-X [pii] AID - 10.1016/j.virol.2007.03.020 [doi] PST - ppublish SO - Virology. 2007 Aug 1;364(2):342-54. doi: 10.1016/j.virol.2007.03.020. Epub 2007 Apr 16.