{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:16:55Z","timestamp":1758709015894},"reference-count":71,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,1,15]],"date-time":"2011-01-15T00:00:00Z","timestamp":1295049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The classical nuclear factor kappa B (NF-\u03baB) signaling pathway is an important regulator of inflammation and innate immunity that is activated by a wide variety of stimuli, including virus infection, tumor necrosis factor alpha (TNF-\u03b1), and interleukin 1\u03b2 (IL-1\u03b2). Poxviruses, including vaccinia virus (VV) and ectromelia virus, encode multiple proteins that function in immune evasion. Recently, a growing number of genes encoded by poxviruses have been shown to target and disrupt the NF-\u03baB signaling pathway. To determine if additional gene products that interfere with NF-\u03baB signaling existed, we used a vaccinia virus deletion mutant, VV811, which is missing 55 open reading frames lacking all known inhibitors of TNF-\u03b1-induced NF-\u03baB activation. Immunofluorescence analysis of HeLa cells treated with TNF-\u03b1 and IL-1\u03b2 revealed that NF-\u03baB translocation to the nucleus was inhibited in VV811-infected cells. This was further confirmed through Western blotting of cytoplasmic and nuclear extracts for NF-\u03baB. Additionally, VV811 infection inhibited TNF-\u03b1-induced I\u03baB\u03b1 degradation. In contrast to vaccinia virus strain Copenhagen (VVCop)-infected cells, VV811 infection resulted in the dramatic accumulation of phosphorylated I\u03baB\u03b1. Correspondingly, coimmunoprecipitation assays demonstrated that the NF-\u03baB-inhibitory I\u03baB\u03b1-p65-p50 complex was intact in VV811-infected cells. Significantly, cells treated with 1-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -arabinofuranosylcytosine, an inhibitor of poxvirus late gene expression, demonstrated that an additional vaccinia virus late gene was involved in the stabilization of I\u03baB\u03b1. Overall, this work indicates that unidentified inhibitors of NF-\u03baB exist in vaccinia virus. The complex inhibition of NF-\u03baB by vaccinia virus illustrates the importance of NF-\u03baB activation in the antiviral response.\n          <\/jats:p>","DOI":"10.1128\/jvi.01267-10","type":"journal-article","created":{"date-parts":[[2010,10,28]],"date-time":"2010-10-28T03:20:07Z","timestamp":1288236007000},"page":"883-894","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["A Vaccinia Virus Deletion Mutant Reveals the Presence of Additional Inhibitors of NF-\u03baB"],"prefix":"10.1128","volume":"85","author":[{"given":"Katharine","family":"Fagan-Garcia","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.8.6.643"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3140380"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.6.3301-3310.1993"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.10.1899"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308068200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010533200"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.160027697"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878466"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040022"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1586"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82772-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1156903"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-168203"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(75)90139-2"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.43.1.136-149.1982"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400567200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1657408"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.19.2.3149"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.12.1339"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00935-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90294-2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000128"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021652"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3859"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.020"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/365182a0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11918"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209941"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.09.048"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.05.044"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37355-6"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35741-7"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801617105"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.860"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.19.9683"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.01.016"},{"key":"e_1_3_2_38_2","first-page":"2637","year":"1996","unstructured":"Moss, B. 1996. 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