title: Strategies of NF-κB signaling modulation by ectromelia virus in BALB/3T3 murine fibroblasts.
abstract: Nuclear factor κB (NF-κB) is a pleiotropic transcription factor that regulates the expression of immune response genes. NF-κB signaling can be disrupted by pathogens that prevent host immune response. In this work, we examined the influence of ectromelia (mousepox) virus (ECTV) on NF-κB signaling in murine BALB/3T3 fibroblasts. Activation of NF-κB via tumor necrosis factor (TNF) receptor 1 (TNFR1) in these cells induces proinflammatory cytokine secretion. We show that ECTV does not recruit NF-κB to viral factories or induce NF-κB nuclear translocation in BALB/3T3 cells. Additionally, ECTV counteracts TNF-α-induced p65 NF-κB nuclear translocation during the course of infection. Inhibition of TNF-α-induced p65 nuclear translocation was also observed in neighboring cells that underwent fusion with ECTV-infected cells. ECTV inhibits the key step of NF-κB activation, i.e. Ser32 phosphorylation and degradation of inhibitor κBα (IκBα) induced by TNF-α. We also observed that ECTV prevents TNF-α-induced Ser536 of p65 phosphorylation in BALB/3T3 cells. Studying TNFR1 signaling provides information about regulation of inflammatory response and cell survival. Unraveling poxviral immunomodulatory strategies may be helpful in drug target identification as well as in vaccine development.
authors.affiliation: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, 02-786 Warsaw, Poland. Electronic address: justyna_struzik@sggw.pl.
authors.forename: Justyna
authors.initials: J
authors.lastname: Struzik
authors.affiliation: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, 02-786 Warsaw, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Szulc-Dąbrowska
authors.affiliation: Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, 02-776 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Winnicka
authors.affiliation: Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, 02-786 Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Niemiałtowski
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D004481:Ectromelia virus / Q000502:physiology*; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D020672:I-kappa B Proteins / Q000378:metabolism; D057131:Immune Evasion; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha
keywords: Ectromelia virus; Fibroblasts; NF-κB; TNFR1