{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:47:37Z","timestamp":1791103657611,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enterovirus 71 (EV71), a single, positive-stranded RNA virus, has been regarded as the most important neurotropic enterovirus after the eradication of the poliovirus. EV71 infection can cause hand, foot, and mouth disease or herpangina. Cytokine storm with elevated levels of proinflammatory and inflammatory cytokines, including TNF-\u03b1, has been proposed to explain the pathogenesis of EV71-induced disease. TNF-\u03b1\u2013mediated NF-\u03baB signaling pathway plays a key role in inflammatory response. We hypothesized that EV71 might also moderate host inflammation by interfering with this pathway. In this study, we tested this hypothesis and identified EV71 2C protein as an antagonist of TNF-\u03b1\u2013mediated activation of NF-\u03baB signaling pathway. Expression of 2C protein significantly reduced TNF-\u03b1\u2013mediated NF-\u03baB activation in 293T cells as measured by gene reporter and gel mobility shift assays. Furthermore, overexpression of TNFR-associated factor 2-, MEK kinase 1-, I\u03baB kinase (IKK)\u03b1-, or IKK\u03b2-induced NF-\u03baB activation, but not constitutively active mutant of IKK\u03b2 (IKK\u03b2 SS\/EE)-induced NF-\u03baB activation, was inhibited by 2C protein. These data together suggested that the activation of IKK\u03b2 is most likely targeted by 2C; this notion was further strengthened by immunoblot detection of IKK\u03b2 phosphorylation and I\u03baB\u03b1 phosphorylation and degradation. Coimmunoprecipitation and colocalization of 2C and IKK\u03b2 expressed in mammalian cells provided compelling evidence that 2C interacts with IKK\u03b2. Collectively, our data indicate that EV71 2C protein inhibits IKK\u03b2 activation and thus blocks NF-\u03baB activation.<\/jats:p>","DOI":"10.4049\/jimmunol.1100285","type":"journal-article","created":{"date-parts":[[2011,8,2]],"date-time":"2011-08-02T00:23:08Z","timestamp":1312244588000},"page":"2202-2212","source":"Crossref","is-referenced-by-count":75,"title":["Enterovirus 71 2C Protein Inhibits TNF-\u03b1\u2013Mediated Activation of NF-\u03baB by Suppressing I\u03baB Kinase \u03b2 Phosphorylation"],"prefix":"10.1093","volume":"187","author":[{"given":"Zhenhua","family":"Zheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Mao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingke","family":"Bai","sequence":"additional","affiliation":[{"name":"Beijing Institute of Infectious Diseases, Beijing 302 Hospital , Beijing, 100045 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anhui Medical University , Hefei, 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panyong","family":"Mao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Infectious Diseases, Beijing 302 Hospital , Beijing, 100045 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxue","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan, 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,1]]},"reference":[{"key":"2025032410324151000_r1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/rmv.538","article-title":"Genetic evolution of enterovirus 71: epidemiological and pathological implications","volume":"17","author":"Bible","year":"2007","journal-title":"Rev. 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