title: The C11R gene, which encodes the vaccinia virus growth factor, is partially responsible for MVA-induced NF-κB and ERK2 activation.
abstract: MVA is an attenuated strain of vaccinia virus (VACV) that is a popular vaccine vector. MVA infection activates NF-κB. For 293T cells, it is known that MVA early gene expression activates extracellular signal-regulated kinase 2 (ERK2), resulting in NF-κB activation. However, other viral and cellular mechanisms responsible for this event are ill defined. The data presented here show that the epidermal growth factor receptor (EGFR) is at least one apical trigger in this pathway: ERK2 and NF-κB activation was diminished when MVA infections occurred in cells devoid of the EGFR (CHO K1 cells) or in the presence of a drug that inhibits EGFR activation (AG1478) in 293T cells. The expression of dominant negative Ras or Raf proteins still permitted NF-κB activation, suggesting that a nonclassical EGFR-based signal transduction pathway triggered ERK2-NF-κB activation. C11R is an early gene present in MVA and other orthopoxviruses. It encodes the soluble, secreted vaccinia virus growth factor (VGF), a protein that binds to and stimulates the EGFR. Here it was observed that NF-κB was activated in 293T cells transfected with a plasmid encoding the C11R gene. Silencing by small interfering RNA (siRNA) or deletion of the C11R gene (MVAΔC11R) reduced both MVA-induced ERK2 and NF-κB activation in 293T cells or the keratinocyte line Hacat, suggesting that this mechanism of MVA-induced NF-κB activation may be common for several cell types.
authors: Department of Microbiology, College of Medicine, University of Illinois, Urbana, Illinois, USA.
authors: Stefani
authors: S
authors: Martin
authors: Daniel T
authors: DT
authors: Harris
authors: Joanna
authors: J
authors: Shisler
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D066246:ErbB Receptors / Q000378:metabolism; D017353:Gene Deletion; D005814:Genes, Viral; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics*; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C560489:MVA vaccine; D016328:NF-kappa B; D034741:RNA, Small Interfering; D019444:Vaccines, DNA; D014765:Viral Vaccines; D066246:ErbB Receptors; D048490:raf Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D018631:ras Proteins