{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:11:05Z","timestamp":1789639865307,"version":"4.0.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108263h0001"],"award-info":[{"award-number":["20fk0108263h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108518h0001"],"award-info":[{"award-number":["20fk0108518h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108263h0001"],"award-info":[{"award-number":["20fk0108263h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108518h0001"],"award-info":[{"award-number":["20fk0108518h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108263h0001"],"award-info":[{"award-number":["20fk0108263h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108296s0101"],"award-info":[{"award-number":["20fk0108296s0101"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20fk0108518h0001"],"award-info":[{"award-number":["20fk0108518h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF6 is an antagonist of interferon (IFN)-mediated antiviral signaling, achieved through the prevention of STAT1 nuclear localization. However, the exact mechanism through which ORF6 prevents STAT1 nuclear trafficking remains unclear. Herein, we demonstrate that ORF6 directly binds to STAT1 with or without IFN stimulation, resulting in the nuclear exclusion of STAT1. ORF6 also recognizes importin \u03b1 subtypes with different modes, in particular, high affinity to importin \u03b11 but a low affinity to importin \u03b15. Although ORF6 potentially disrupts the importin \u03b1\/importin \u03b21-mediated nuclear transport, thereby suppressing the nuclear translocation of the other classical nuclear localization signal-containing cargo proteins, the inhibitory effect of ORF6 is modest when compared with that of STAT1. The results indicate that the drastic nuclear exclusion of STAT1 is attributed to the specific binding with ORF6, which is a distinct strategy for the importin \u03b11-mediated pathway. Combined with the results from a newly-produced replicon system and a hamster model, we conclude that SARS-CoV-2 ORF6 acts as a virulence factor via regulation of nucleocytoplasmic trafficking to accelerate viral replication, resulting in disease progression.<\/jats:p>","DOI":"10.1038\/s42003-022-03427-4","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T10:05:28Z","timestamp":1652954728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["SARS-CoV-2 ORF6 disrupts nucleocytoplasmic trafficking to advance viral replication"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4016-1119","authenticated-orcid":false,"given":"Yoichi","family":"Miyamoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-8256","authenticated-orcid":false,"given":"Yusuke","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-0666","authenticated-orcid":false,"given":"Masaru","family":"Koido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Otani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-5188","authenticated-orcid":false,"given":"Kohji","family":"Moriishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Kamatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Yoneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-3102","authenticated-orcid":false,"given":"Toru","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0123-3060","authenticated-orcid":false,"given":"Masahiro","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"3427_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273 (2020).","journal-title":"Nature"},{"key":"3427_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/22221751.2020.1719902","volume":"9","author":"JF Chan","year":"2020","unstructured":"Chan, J. F. et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect. 9, 221\u2013236 (2020).","journal-title":"Emerg. Microbes Infect."},{"key":"3427_CR3","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","volume":"395","author":"R Lu","year":"2020","unstructured":"Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565\u2013574 (2020).","journal-title":"Lancet"},{"key":"3427_CR4","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","volume":"181","author":"D Kim","year":"2020","unstructured":"Kim, D. et al. The Architecture of SARS-CoV-2 Transcriptome. Cell 181, 914\u2013921.e910 (2020).","journal-title":"Cell"},{"key":"3427_CR5","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jpha.2020.03.001","volume":"10","author":"X Li","year":"2020","unstructured":"Li, X., Geng, M., Peng, Y., Meng, L. & Lu, S. Molecular immune pathogenesis and diagnosis of COVID-19. J. Pharm. Anal. 10, 102\u2013108 (2020).","journal-title":"J. Pharm. Anal."},{"key":"3427_CR6","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1080\/22221751.2020.1780953","volume":"9","author":"CK Yuen","year":"2020","unstructured":"Yuen, C. K. et al. SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg. Microbes Infect. 9, 1418\u20131428 (2020).","journal-title":"Emerg. Microbes Infect."},{"key":"3427_CR7","doi-asserted-by":"publisher","first-page":"9812","DOI":"10.1128\/JVI.01012-07","volume":"81","author":"M Frieman","year":"2007","unstructured":"Frieman, M. et al. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum\/Golgi membrane. J. Virol. 81, 9812\u20139824 (2007).","journal-title":"J. Virol."},{"key":"3427_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17665-9","volume":"11","author":"X Lei","year":"2020","unstructured":"Lei, X. et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810 (2020).","journal-title":"Nat. Commun."},{"key":"3427_CR9","doi-asserted-by":"publisher","first-page":"198074","DOI":"10.1016\/j.virusres.2020.198074","volume":"286","author":"JY Li","year":"2020","unstructured":"Li, J. Y. et al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Res. 286, 198074 (2020).","journal-title":"Virus Res."},{"key":"3427_CR10","doi-asserted-by":"publisher","first-page":"28344","DOI":"10.1073\/pnas.2016650117","volume":"117","author":"L Miorin","year":"2020","unstructured":"Miorin, L. et al. SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc. Natl Acad. Sci. USA 117, 28344\u201328354 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3427_CR11","doi-asserted-by":"publisher","first-page":"108234","DOI":"10.1016\/j.celrep.2020.108234","volume":"33","author":"H Xia","year":"2020","unstructured":"Xia, H. et al. Evasion of Type I Interferon by SARS-CoV-2. Cell Rep. 33, 108234 (2020).","journal-title":"Cell Rep."},{"key":"3427_CR12","doi-asserted-by":"publisher","first-page":"108916","DOI":"10.1016\/j.celrep.2021.108916","volume":"34","author":"I Kimura","year":"2021","unstructured":"Kimura, I. et al. Sarbecovirus ORF6 proteins hamper induction of interferon signaling. Cell Rep. 34, 108916 (2021).","journal-title":"Cell Rep."},{"key":"3427_CR13","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nri1604","volume":"5","author":"LC Platanias","year":"2005","unstructured":"Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5, 375\u2013386 (2005).","journal-title":"Nat. Rev. Immunol."},{"key":"3427_CR14","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.3389\/fimmu.2018.01135","volume":"9","author":"A Michalska","year":"2018","unstructured":"Michalska, A., Blaszczyk, K., Wesoly, J. & Bluyssen, H. A. R. A positive feedback amplifier circuit that regulates interferon (IFN)-stimulated gene expression and controls type I and type II IFN responses. Front. Immunol. 9, 1135 (2018).","journal-title":"Front. Immunol."},{"key":"3427_CR15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.tcb.2010.05.001","volume":"20","author":"S Walde","year":"2010","unstructured":"Walde, S. & Kehlenbach, R. H. The Part and the Whole: functions of nucleoporins in nucleocytoplasmic transport. Trends Cell Biol. 20, 461\u2013469 (2010).","journal-title":"Trends Cell Biol."},{"key":"3427_CR16","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.tcb.2008.07.009","volume":"18","author":"MA D\u2019Angelo","year":"2008","unstructured":"D\u2019Angelo, M. A. & Hetzer, M. W. Structure, dynamics and function of nuclear pore complexes. Trends Cell Biol. 18, 456\u2013466 (2008).","journal-title":"Trends Cell Biol."},{"key":"3427_CR17","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1016\/j.bbamcr.2010.10.014","volume":"1813","author":"YM Chook","year":"2011","unstructured":"Chook, Y. M. & Suel, K. E. Nuclear import by karyopherin-betas: recognition and inhibition. Biochim. Biophys. Acta 1813, 1593\u20131606 (2011).","journal-title":"Biochim. Biophys. Acta"},{"key":"3427_CR18","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1042\/BJ20141186","volume":"466","author":"RA Pumroy","year":"2015","unstructured":"Pumroy, R. A. & Cingolani, G. Diversification of importin-\u03b1 isoforms in cellular trafficking and disease states. Biochem. J. 466, 13\u201328 (2015).","journal-title":"Biochem. J."},{"key":"3427_CR19","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/s00412-005-0043-3","volume":"115","author":"AS Madrid","year":"2006","unstructured":"Madrid, A. S. & Weis, K. Nuclear transport is becoming crystal clear. Chromosoma 115, 98\u2013109 (2006).","journal-title":"Chromosoma"},{"key":"3427_CR20","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1016\/j.bbamcr.2010.10.013","volume":"1813","author":"M Marfori","year":"2011","unstructured":"Marfori, M. et al. Molecular basis for specificity of nuclear import and prediction of nuclear localization. Biochim Biophys. Acta 1813, 1562\u20131577 (2011).","journal-title":"Biochim Biophys. Acta"},{"key":"3427_CR21","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.bbagrm.2012.01.015","volume":"1819","author":"Y Miyamoto","year":"2012","unstructured":"Miyamoto, Y., Boag, P. R., Hime, G. R. & Loveland, K. L. Regulated nucleocytoplasmic transport during gametogenesis. Biochim Biophys. Acta 1819, 616\u2013630 (2012).","journal-title":"Biochim Biophys. Acta"},{"key":"3427_CR22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1093\/jb\/mvw036","volume":"160","author":"Y Miyamoto","year":"2016","unstructured":"Miyamoto, Y., Yamada, K. & Yoneda, Y. Importin \u03b1: a key molecule in nuclear transport and non-transport functions. J. Biochem. 160, 69\u201375 (2016).","journal-title":"J. Biochem."},{"key":"3427_CR23","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.tcb.2004.07.016","volume":"14","author":"DS Goldfarb","year":"2004","unstructured":"Goldfarb, D. S., Corbett, A. H., Mason, D. A., Harreman, M. T. & Adam, S. A. Importin \u03b1: a multipurpose nuclear-transport receptor. Trends Cell Biol. 14, 505\u2013514 (2004).","journal-title":"Trends Cell Biol."},{"key":"3427_CR24","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s00239-009-9215-8","volume":"68","author":"DA Mason","year":"2009","unstructured":"Mason, D. A., Stage, D. E. & Goldfarb, D. S. Evolution of the metazoan-specific importin \u03b1 gene family. J. Mol. Evol. 68, 351\u2013365 (2009).","journal-title":"J. Mol. Evol."},{"key":"3427_CR25","doi-asserted-by":"publisher","first-page":"7067","DOI":"10.1093\/emboj\/16.23.7067","volume":"16","author":"T Sekimoto","year":"1997","unstructured":"Sekimoto, T., Imamoto, N., Nakajima, K., Hirano, T. & Yoneda, Y. Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J. 16, 7067\u20137077 (1997).","journal-title":"EMBO J."},{"key":"3427_CR26","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/emboj\/21.7.1754","volume":"21","author":"KM McBride","year":"2002","unstructured":"McBride, K. M., Banninger, G., McDonald, C. & Reich, N. C. Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-\u03b1. EMBO J. 21, 1754\u20131763 (2002).","journal-title":"EMBO J."},{"key":"3427_CR27","doi-asserted-by":"publisher","first-page":"28193","DOI":"10.1074\/jbc.M303571200","volume":"278","author":"K Melen","year":"2003","unstructured":"Melen, K. et al. Importin \u03b1 nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. J. Biol. Chem. 278, 28193\u201328200 (2003).","journal-title":"J. Biol. Chem."},{"key":"3427_CR28","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jmb.2010.07.013","volume":"402","author":"J Nardozzi","year":"2010","unstructured":"Nardozzi, J., Wenta, N., Yasuhara, N., Vinkemeier, U. & Cingolani, G. Molecular basis for the recognition of phosphorylated STAT1 by importin \u03b15. J. Mol. Biol. 402, 83\u2013100 (2010).","journal-title":"J. Mol. Biol."},{"key":"3427_CR29","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","volume":"583","author":"DE Gordon","year":"2020","unstructured":"Gordon, D. E. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583, 459\u2013468 (2020).","journal-title":"Nature"},{"key":"3427_CR30","doi-asserted-by":"publisher","first-page":"e00065","DOI":"10.1128\/mBio.00065-21","volume":"12","author":"A Addetia","year":"2021","unstructured":"Addetia, A. et al. SARS-CoV-2 ORF6 disrupts bidirectional nucleocytoplasmic transport through interactions with Rae1 and Nup98. mBio 12, e00065\u201300021 (2021).","journal-title":"mBio"},{"key":"3427_CR31","doi-asserted-by":"publisher","first-page":"6159","DOI":"10.1128\/JVI.06872-11","volume":"86","author":"T Abe","year":"2012","unstructured":"Abe, T. et al. CD44 participates in IP-10 induction in cells in which hepatitis C virus RNA is replicating, through an interaction with Toll-like receptor 2 and hyaluronan. J. Virol. 86, 6159\u20136170 (2012).","journal-title":"J. Virol."},{"key":"3427_CR32","doi-asserted-by":"crossref","unstructured":"Riojas M. A. et al. A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein. bioRxiv: the preprint server for biology, 2020.2006.2009.134460 (2020).","DOI":"10.1101\/2020.06.09.134460"},{"key":"3427_CR33","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1083\/jcb.200312008","volume":"165","author":"Y Miyamoto","year":"2004","unstructured":"Miyamoto, Y. et al. Cellular stresses induce the nuclear accumulation of importin \u03b1 and cause a conventional nuclear import block. J. Cell Biol. 165, 617\u2013623 (2004).","journal-title":"J. Cell Biol."},{"key":"3427_CR34","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/sj.cdd.4401432","volume":"11","author":"M Kodiha","year":"2004","unstructured":"Kodiha, M., Chu, A., Matusiewicz, N. & Stochaj, U. Multiple mechanisms promote the inhibition of classical nuclear import upon exposure to severe oxidative stress. Cell Death Differ. 11, 862\u2013874 (2004).","journal-title":"Cell Death Differ."},{"key":"3427_CR35","doi-asserted-by":"publisher","first-page":"15942","DOI":"10.1074\/jbc.M500814200","volume":"280","author":"R Fagerlund","year":"2005","unstructured":"Fagerlund, R., Kinnunen, L., Kohler, M., Julkunen, I. & Melen, K. NF-\u03baB is transported into the nucleus by importin \u03b13 and importin \u03b14. J. Biol. Chem. 280, 15942\u201315951 (2005).","journal-title":"J. Biol. Chem."},{"key":"3427_CR36","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.bbamcr.2007.12.006","volume":"1783","author":"R Depping","year":"2008","unstructured":"Depping, R. et al. Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha\/beta pathway. Biochim Biophys. Acta 1783, 394\u2013404 (2008).","journal-title":"Biochim Biophys. Acta"},{"key":"3427_CR37","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/tra.12097","volume":"14","author":"P Liang","year":"2013","unstructured":"Liang, P. et al. KPNB1, XPO7 and IPO8 mediate the translocation ofNF-\u03baB\/p65 into the nucleus. Traffic 14, 1132\u20131143 (2013).","journal-title":"Traffic"},{"key":"3427_CR38","doi-asserted-by":"publisher","first-page":"4606","DOI":"10.1111\/j.1432-1033.2004.04423.x","volume":"271","author":"T Meyer","year":"2004","unstructured":"Meyer, T. & Vinkemeier, U. Nucleocytoplasmic shuttling of STAT transcription factors. Eur. J. Biochem. 271, 4606\u20134612 (2004).","journal-title":"Eur. J. Biochem."},{"key":"3427_CR39","doi-asserted-by":"publisher","first-page":"9373","DOI":"10.1073\/pnas.0903487106","volume":"106","author":"H Cheon","year":"2009","unstructured":"Cheon, H. & Stark, G. R. Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Proc. Natl Acad. Sci. USA 106, 9373\u20139378 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3427_CR40","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.1038\/emboj.2013.203","volume":"32","author":"H Cheon","year":"2013","unstructured":"Cheon, H. et al. IFN\u03b2-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 32, 2751\u20132763 (2013).","journal-title":"EMBO J."},{"key":"3427_CR41","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.bbrc.2020.11.115","volume":"536","author":"K Kato","year":"2020","unstructured":"Kato, K. et al. Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex. Biochem Biophys. Res Commun. 536, 59\u201366 (2020).","journal-title":"Biochem Biophys. Res Commun."},{"key":"3427_CR42","doi-asserted-by":"publisher","first-page":"750969","DOI":"10.3389\/fimmu.2021.750969","volume":"12","author":"W Li","year":"2021","unstructured":"Li, W. et al. SARS-CoV-2 Nsp5 activates NF-\u03baB pathway by upregulating SUMOylation of MAVS. Front. Immunol. 12, 750969 (2021).","journal-title":"Front. Immunol."},{"key":"3427_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92941-2","volume":"11","author":"CM Su","year":"2021","unstructured":"Su, C. M., Wang, L. & Yoo, D. Activation of NF-\u03baB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2. Sci. Rep. 11, 13464 (2021).","journal-title":"Sci. Rep."},{"key":"3427_CR44","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1247\/csf.20.151","volume":"20","author":"Y Kishiro","year":"1995","unstructured":"Kishiro, Y., Kagawa, M., Naito, I. & Sado, Y. A novel method of preparing rat-monoclonal antibody-producing hybridomas by using rat medial iliac lymph node cells. Cell Struct. Funct. 20, 151\u2013156 (1995).","journal-title":"Cell Struct. Funct."},{"key":"3427_CR45","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.virol.2007.04.029","volume":"366","author":"P Kumar","year":"2007","unstructured":"Kumar, P. et al. The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein. Virology 366, 293\u2013303 (2007).","journal-title":"Virology"},{"key":"3427_CR46","doi-asserted-by":"publisher","first-page":"31017","DOI":"10.1074\/jbc.271.49.31017","volume":"271","author":"T Sekimoto","year":"1996","unstructured":"Sekimoto, T., Nakajima, K., Tachibana, T., Hirano, T. & Yoneda, Y. Interferon-gamma-dependent nuclear import of Stat1 is mediated by the GTPase activity of Ran\/TC4. J. Biol. Chem. 271, 31017\u201331020 (1996).","journal-title":"J. Biol. Chem."},{"key":"3427_CR47","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1016\/j.bbamcr.2015.07.017","volume":"1853","author":"C Kimoto","year":"2015","unstructured":"Kimoto, C. et al. Functional characterization of importin \u03b18 as a classical nuclear localization signal receptor. Biochim Biophys. Acta 1853, 2676\u20132683 (2015).","journal-title":"Biochim Biophys. Acta"},{"key":"3427_CR48","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/ni1243","volume":"6","author":"T Kawai","year":"2005","unstructured":"Kawai, T. et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 6, 981\u2013988 (2005).","journal-title":"Nat. Immunol."},{"key":"3427_CR49","doi-asserted-by":"publisher","first-page":"5833","DOI":"10.1093\/emboj\/cdf569","volume":"21","author":"Y Miyamoto","year":"2002","unstructured":"Miyamoto, Y. et al. Importin \u03b1 can migrate into the nucleus in an importin \u03b2- and Ran-independent manner. EMBO J. 21, 5833\u20135842 (2002).","journal-title":"EMBO J."},{"key":"3427_CR50","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.dib.2016.03.080","volume":"7","author":"Y Miyamoto","year":"2016","unstructured":"Miyamoto, Y. & Oka, M. Data on dimer formation between importin \u03b1 subtypes. Data Brief. 7, 1248\u20131253 (2016).","journal-title":"Data Brief."},{"key":"3427_CR51","doi-asserted-by":"publisher","first-page":"105268","DOI":"10.1016\/j.antiviral.2022.105268","volume":"199","author":"T Tanaka","year":"2022","unstructured":"Tanaka, T. et al. Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening. Antivir. Res. 199, 105268 (2022).","journal-title":"Antivir. Res."},{"key":"3427_CR52","doi-asserted-by":"publisher","first-page":"16224","DOI":"10.1096\/fj.202000768RR","volume":"34","author":"Y Miyamoto","year":"2020","unstructured":"Miyamoto, Y. et al. Genetic loss of importin \u03b14 causes abnormal sperm morphology and impacts on male fertility in mouse. Faseb J. 34, 16224\u201316242 (2020).","journal-title":"Faseb J."},{"key":"3427_CR53","doi-asserted-by":"publisher","first-page":"e00658","DOI":"10.1128\/mSphere.00658-20","volume":"5","author":"C Shema Mugisha","year":"2020","unstructured":"Shema Mugisha, C. et al. A Simplified Quantitative Real-Time PCR Assay for Monitoring SARS-CoV-2 Growth in Cell Culture. mSphere 5, e00658\u201300620 (2020).","journal-title":"mSphere"},{"key":"3427_CR54","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1128\/JVI.03162-12","volume":"87","author":"J Edmonds","year":"2013","unstructured":"Edmonds, J. et al. A novel bacterium-free method for generation of flavivirus infectious DNA by circular polymerase extension reaction allows accurate recapitulation of viral heterogeneity. J. Virol. 87, 2367\u20132372 (2013).","journal-title":"J. Virol."},{"key":"3427_CR55","doi-asserted-by":"publisher","first-page":"109014","DOI":"10.1016\/j.celrep.2021.109014","volume":"35","author":"S Torii","year":"2021","unstructured":"Torii, S. et al. Establishment of a reverse genetics system for SARS-CoV-2 using circular polymerase extension reaction. Cell Rep. 35, 109014 (2021).","journal-title":"Cell Rep."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03427-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03427-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03427-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T21:36:59Z","timestamp":1700602619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03427-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3427"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03427-4","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,19]]},"assertion":[{"value":"29 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"483"}}