{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:30Z","timestamp":1787016690976,"version":"build-2736575974"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"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":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The NF-\u03baB signaling pathway plays a critical role in inflammation and innate immunity. Consequently, many viruses have evolved strategies to inhibit NF-\u03baB in order to facilitate replication and evasion of the host immune response. Recently, we determined that ectromelia virus, the causative agent of mousepox, contains a family of four BTB\/kelch proteins that interact with cullin-3-based ubiquitin ligases. We demonstrate here that expression of EVM150, one of the four BTB\/kelch proteins, inhibited NF-\u03baB activation induced by tumor necrosis factor alpha (TNF-\u03b1) and interleukin-1\u03b2 (IL-1\u03b2). Although EVM150 inhibited NF-\u03baB p65 nuclear translocation, I\u03baB\u03b1 degradation was observed, indicating that EVM150 functioned downstream of I\u03baB\u03b1 degradation. Significantly, expression of the BTB-only domain of EVM150 blocked NF-\u03baB activation, demonstrating that EVM150 functioned independently of the kelch domain and its role as an adapter for cullin-3-based ubiquitin ligases. Furthermore, cullin-3 knockdown by small interfering RNA demonstrated that cullin-3-based ubiquitin ligases are dispensable for TNF-\u03b1-induced NF-\u03baB activation. Interestingly, nuclear translocation of IRF3 and STAT1 still occurred in the presence of EVM150, indicating that EVM150 prevented NF-\u03baB nuclear translocation specifically. In addition to identifying EVM150 as an inhibitor of the NF-\u03baB pathway, this study provides new insights into the role of BTB\/kelch proteins during virus infection.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    With the exception of virulence studies, little work has been done to determine the role of poxviral BTB\/kelch proteins during infection. This study, for the first time, has identified a mechanism for the ectromelia virus BTB\/kelch protein EVM150. Here, we show that EVM150 is a novel inhibitor of the cellular NF-\u03baB pathway, an important component of the antiviral response. This study adds EVM150 to the growing list of NF-\u03baB inhibitors in poxviruses and provides new insights into the role of BTB\/kelch proteins during virus infection.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02923-13","type":"journal-article","created":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T00:44:12Z","timestamp":1392252252000},"page":"4853-4865","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Ectromelia Virus Encodes a BTB\/kelch Protein, EVM150, That Inhibits NF-\u03baB Signaling"],"prefix":"10.1128","volume":"88","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Burles","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianne","family":"Couturier","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal M. 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