The classical Nuclear Factor kappa B (NF-B) signaling pathway is an important regulator of inflammation and innate immune responses. Poxviruses, including vaccinia virus, encode multiple immune evasion proteins, including a growing number of NF-B inhibitors. To determine if additional vaccinia virus gene products disrupted NF-B signaling, we utilized VV811, a mutant virus missing 55 open reading frames and devoid of the known inhibitors of TNF-induced NF-B activation. NF-B nuclear translocation was inhibited in VV811 infected cells stimulated with TNF.
Furthermore, VV811 infection suppressed IB degradation and resulted in accumulation of phosphorylated IB in cells stimulated with TNF. Coimmunoprecipitation
assays demonstrated that the inhibitory IB-p65-p50
complex was intact in VV811 infected cells, and, significantly, treatment with AraC revealed the involvement of late protein synthesis in stabilization of IB. This work indicates that unidentified inhibitors of NF-B exist in vaccinia virus and illustrates the importance of NF-B activation in the antiviral response. / Virology
Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1246 |
Date | 11 1900 |
Creators | Fagan-Garcia, Katharine |
Contributors | Barry, Michele (Medical Microbiology and Immunology), Smiley, James (Medical Microbiology and Immunology), Foley, Edan (Medical Microbiology and Immunology), Baksh, Shairaz (Pediatrics) |
Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
Language | en_US |
Detected Language | English |
Type | Thesis |
Format | 26771162 bytes, application/pdf |
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