{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:14:48Z","timestamp":1791321288413,"version":"4.3.1"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)\/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the I\u03baB kinase (IKK)-related kinase IKK\u03b5 but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKK\u03b5 interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKK\u03b5 colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKK\u03b5 (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKK\u03b5 as a novel target of arenavirus NP. Engagement of NP seems to sequester IKK\u03b5 in an inactive complex. Considering the important functions of IKK\u03b5 in innate antiviral immunity and other cellular processes, the NP-IKK\u03b5 interaction likely plays a crucial role in arenavirus-host interaction.<\/jats:p>","DOI":"10.1128\/jvi.00187-12","type":"journal-article","created":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:16:40Z","timestamp":1335399400000},"page":"7728-7738","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":131,"title":["Arenavirus Nucleoprotein Targets Interferon Regulatory Factor-Activating Kinase IKK\u03b5"],"prefix":"10.1128","volume":"86","author":[{"given":"Christelle","family":"Pythoud","sequence":"first","affiliation":[{"name":"Institute of Microbiology University Hospital Center and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. W. Shanaka I.","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pasqual","sequence":"additional","affiliation":[{"name":"Institute of Microbiology University Hospital Center and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Rothenberger","sequence":"additional","affiliation":[{"name":"Institute of Microbiology University Hospital Center and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Mart\u00ednez-Sobrido","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kunz","sequence":"additional","affiliation":[{"name":"Institute of Microbiology University Hospital Center and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2861"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.5.2866-2872.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.052"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v2112443"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.12.7673-7681.2005"},{"key":"e_1_3_2_7_2","first-page":"1791","volume-title":"Fields virology","author":"Buchmeier MJ","year":"2007","unstructured":"BuchmeierMJ de la TorreJC PetersCJ. 2007. Arenaviridae: the viruses and their replication, p 1791\u20131828. In KnipeDL HowleyPM (ed), Fields virology, 4th ed. 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