{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:24:29Z","timestamp":1793075069752,"version":"4.5.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["R\u2019Equip 316030_170799\/1"],"award-info":[{"award-number":["R\u2019Equip 316030_170799\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_179256\/1"],"award-info":[{"award-number":["31003A_179256\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting the persistence of human adenovirus (AdV), a virus that can kill immunosuppressed patients. Cell biological analyses, genetics and chemical interference demonstrate that one of five AdV membrane proteins, the E3-19K glycoprotein specifically triggers the unfolded protein response (UPR) sensor IRE1\u03b1 in the endoplasmic reticulum (ER), but not other UPR sensors, such as protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). The E3-19K lumenal domain activates the IRE1\u03b1 nuclease, which initiates mRNA splicing of X-box binding protein-1 (XBP1). XBP1s binds to the viral E1A-enhancer\/promoter sequence, and boosts E1A transcription, E3-19K levels and lytic infection. Inhibition of IRE1\u03b1 nuclease interrupts the five components feedforward loop, E1A, E3-19K, IRE1\u03b1, XBP1s, E1A enhancer\/promoter. This loop sustains persistent infection in the presence of the immune activator interferon, and lytic infection in the absence of interferon.<\/jats:p>","DOI":"10.1038\/s41467-020-15844-2","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T10:27:15Z","timestamp":1587724035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The UPR sensor IRE1\u03b1 and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-607X","authenticated-orcid":false,"given":"Vibhu","family":"Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-3008","authenticated-orcid":false,"given":"Maarit","family":"Suomalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yllza","family":"Jasiqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Hemmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-4262","authenticated-orcid":false,"given":"Louise","family":"Hosie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Gerhard","family":"Burgert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-120X","authenticated-orcid":false,"given":"Urs F.","family":"Greber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"15844_CR1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cell.2009.06.036","volume":"138","author":"HW Virgin","year":"2009","unstructured":"Virgin, H. W., Wherry, E. J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30\u201350 (2009).","journal-title":"Cell"},{"key":"15844_CR2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.coviro.2017.03.001","volume":"23","author":"RE Randall","year":"2017","unstructured":"Randall, R. E. & Griffin, D. E. Within host RNA virus persistence: mechanisms and consequences. Curr. Opin. Virol. 23, 35\u201342 (2017).","journal-title":"Curr. Opin. Virol."},{"key":"15844_CR3","doi-asserted-by":"publisher","first-page":"3551","DOI":"10.1002\/1873-3468.13697","volume":"593","author":"KL Lynch","year":"2019","unstructured":"Lynch, K. L., Gooding, L. R., Garnett-Benson, C., Ornelles, D. A. & Avgousti, D. C. Epigenetics and the dynamics of chromatin during adenovirus infections. FEBS Lett. 593, 3551\u20133570 (2019).","journal-title":"FEBS Lett."},{"key":"15844_CR4","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/0092-8674(86)90076-0","volume":"46","author":"MJ Gething","year":"1986","unstructured":"Gething, M. J., McCammon, K. & Sambrook, J. Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell 46, 939\u2013950 (1986).","journal-title":"Cell"},{"key":"15844_CR5","doi-asserted-by":"publisher","first-page":"6890","DOI":"10.1128\/JVI.79.11.6890-6899.2005","volume":"79","author":"JA Isler","year":"2005","unstructured":"Isler, J. A., Skalet, A. H. & Alwine, J. C. Human cytomegalovirus infection activates and regulates the unfolded protein response. J. Virol. 79, 6890\u20136899 (2005).","journal-title":"J. Virol."},{"key":"15844_CR6","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1128\/JVI.79.3.1379-1388.2005","volume":"79","author":"G Cheng","year":"2005","unstructured":"Cheng, G., Feng, Z. & He, B. Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein. J. Virol. 79, 1379\u20131388 (2005).","journal-title":"J. Virol."},{"key":"15844_CR7","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","volume":"107","author":"H Yoshida","year":"2001","unstructured":"Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. & Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881\u2013891 (2001).","journal-title":"Cell"},{"key":"15844_CR8","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","volume":"11","author":"HP Harding","year":"2003","unstructured":"Harding, H. P. et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11, 619\u2013633 (2003).","journal-title":"Mol. Cell"},{"key":"15844_CR9","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1126\/science.1209038","volume":"334","author":"P Walter","year":"2011","unstructured":"Walter, P. & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081\u20131086 (2011).","journal-title":"Science"},{"key":"15844_CR10","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1146\/annurev-cellbio-101011-155826","volume":"28","author":"A Korennykh","year":"2012","unstructured":"Korennykh, A. & Walter, P. Structural basis of the unfolded protein response. Annu Rev. Cell Dev. Biol. 28, 251\u2013277 (2012).","journal-title":"Annu Rev. Cell Dev. Biol."},{"key":"15844_CR11","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/S0092-8674(00)80369-4","volume":"90","author":"C Sidrauski","year":"1997","unstructured":"Sidrauski, C. & Walter, P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 90, 1031\u20131039 (1997).","journal-title":"Cell"},{"key":"15844_CR12","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.15252\/embj.201490332","volume":"33","author":"J Jurkin","year":"2014","unstructured":"Jurkin, J. et al. The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells. EMBO J. 33, 2922\u20132936 (2014).","journal-title":"EMBO J."},{"key":"15844_CR13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/v12010017","volume":"12","author":"BP Johnston","year":"2019","unstructured":"Johnston, B. P. & McCormick, C. Herpesviruses and the unfolded protein response. Viruses 12, 12\u201317 (2019).","journal-title":"Viruses"},{"key":"15844_CR14","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.tim.2016.02.007","volume":"24","author":"CR King","year":"2016","unstructured":"King, C. R., Zhang, A. & Mymryk, J. S. The persistent mystery of adenovirus persistence. Trends Microbiol. 24, 323\u2013324 (2016).","journal-title":"Trends Microbiol."},{"key":"15844_CR15","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1128\/CMR.00116-13","volume":"27","author":"T Lion","year":"2014","unstructured":"Lion, T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin. Microbiol. Rev. 27, 441\u2013462 (2014).","journal-title":"Clin. Microbiol. Rev."},{"key":"15844_CR16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1089\/hum.2014.001","volume":"25","author":"R Hendrickx","year":"2014","unstructured":"Hendrickx, R. et al. Innate immunity to adenovirus. Hum. Gene Ther. 25, 265\u2013284 (2014).","journal-title":"Hum. Gene Ther."},{"key":"15844_CR17","doi-asserted-by":"publisher","first-page":"e381","DOI":"10.1016\/j.cmi.2015.12.013","volume":"22","author":"K Kosulin","year":"2016","unstructured":"Kosulin, K. et al. Persistence and reactivation of human adenoviruses in the gastrointestinal tract. Clin. Microbiol. Infect. 22, e381\u2013e388 (2016).","journal-title":"Clin. Microbiol. Infect."},{"key":"15844_CR18","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/bmt.2016.321","volume":"52","author":"RE Schultze-Florey","year":"2017","unstructured":"Schultze-Florey, R. E. et al. Persistent recipient-derived human adenovirus (HAdV)-specific T cells promote HAdV control after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 52, 609\u2013611 (2017).","journal-title":"Bone Marrow Transplant."},{"key":"15844_CR19","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1055\/s-0036-1584923","volume":"37","author":"JP Lynch 3rd","year":"2016","unstructured":"Lynch, J. P. 3rd & Kajon, A. E. Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin. Respir. Crit. Care Med. 37, 586\u2013602 (2016).","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"15844_CR20","unstructured":"State of New Jersey Department of Health. Ongoing Adenovirus Outbreaks. (State of New Jersey Department of Health, 2019)."},{"key":"15844_CR21","unstructured":"Berk A. J. Adenoviridae: the viruses and their replication. In: Fields Virology 6th edn, (eds. Knipe, D. M. & Howley, P. M.) (Lippincott Williams & Wilkins, 2013)."},{"key":"15844_CR22","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev-virology-092818-015550","volume":"6","author":"UF Greber","year":"2019","unstructured":"Greber, U. F. & Flatt, J. W. Adenovirus entry: from infection to immunity. Annu Rev. Virol. 6, 177\u2013197 (2019).","journal-title":"Annu Rev. Virol."},{"key":"15844_CR23","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1016\/j.celrep.2019.11.064","volume":"29","author":"M Bauer","year":"2019","unstructured":"Bauer, M. et al. The E3 ubiquitin ligase mind bomb 1 controls adenovirus genome release at the nuclear pore complex. Cell Rep. 29, 3785\u20133795e3788 (2019).","journal-title":"Cell Rep."},{"key":"15844_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1146\/annurev.ge.20.120186.000401","volume":"20","author":"AJ Berk","year":"1986","unstructured":"Berk, A. J. Adenovirus promoters and E1A transactivation. Annu Rev. Genet. 20, 45\u201379 (1986).","journal-title":"Annu Rev. Genet."},{"key":"15844_CR25","doi-asserted-by":"publisher","first-page":"e00390","DOI":"10.1128\/mBio.00390-18","volume":"9","author":"CR King","year":"2018","unstructured":"King, C. R., Zhang, A., Tessier, T. M., Gameiro, S. F. & Mymryk, J. S. Hacking the cell: network intrusion and exploitation by adenovirus E1A. MBio 9, e00390 (2018).","journal-title":"MBio"},{"key":"15844_CR26","doi-asserted-by":"publisher","first-page":"3665","DOI":"10.1073\/pnas.76.8.3665","volume":"76","author":"N Jones","year":"1979","unstructured":"Jones, N. & Shenk, T. An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc. Natl Acad. Sci. USA 76, 3665\u20133669 (1979).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR27","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/0092-8674(79)90333-7","volume":"17","author":"AJ Berk","year":"1979","unstructured":"Berk, A. J., Lee, F., Harrison, T., Williams, J. & Sharp, P. A. Pre-early adenovirus 5 gene product regulates synthesis of early viral messenger RNAs. Cell 17, 935\u2013944 (1979).","journal-title":"Cell"},{"key":"15844_CR28","first-page":"113","volume":"273","author":"SP Fessler","year":"2004","unstructured":"Fessler, S. P., Delgado-Lopez, F. & Horwitz, M. S. Mechanisms of E3 modulation of immune and inflammatory responses. Curr. Top. Microbiol. Immunol. 273, 113\u2013135 (2004).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"15844_CR29","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/08830180490265556","volume":"23","author":"DL Lichtenstein","year":"2004","unstructured":"Lichtenstein, D. L., Toth, K., Doronin, K., Tollefson, A. E. & Wold, W. S. Functions and mechanisms of action of the adenovirus E3 proteins. Int Rev. Immunol. 23, 75\u2013111 (2004).","journal-title":"Int Rev. Immunol."},{"key":"15844_CR30","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1002\/hep.21525","volume":"45","author":"EV Mashalova","year":"2007","unstructured":"Mashalova, E. V. et al. Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells. Hepatology 45, 755\u2013766 (2007).","journal-title":"Hepatology"},{"key":"15844_CR31","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1073\/pnas.86.10.3823","volume":"86","author":"HS Ginsberg","year":"1989","unstructured":"Ginsberg, H. S. et al. Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proc. Natl Acad. Sci. USA 86, 3823\u20133827 (1989).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR32","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S0092-8674(85)80079-9","volume":"41","author":"HG Burgert","year":"1985","unstructured":"Burgert, H. G. & Kvist, S. An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell 41, 987\u2013997 (1985).","journal-title":"Cell"},{"key":"15844_CR33","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/0092-8674(85)90026-1","volume":"43","author":"M Andersson","year":"1985","unstructured":"Andersson, M., Paabo, S., Nilsson, T. & Peterson, P. A. Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance. Cell 43, 215\u2013222 (1985).","journal-title":"Cell"},{"key":"15844_CR34","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1073\/pnas.84.5.1356","volume":"84","author":"HG Burgert","year":"1987","unstructured":"Burgert, H. G., Maryanski, J. L. & Kvist, S. \u201cE3\/19K\u201d protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proc. Natl Acad. Sci. USA 84, 1356\u20131360 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR35","doi-asserted-by":"publisher","first-page":"255","DOI":"10.4049\/jimmunol.0902343","volume":"184","author":"M Sester","year":"2010","unstructured":"Sester, M. et al. Conserved amino acids within the adenovirus 2 E3\/19K protein differentially affect downregulation of MHC class I and MICA\/B proteins. J. Immunol. 184, 255\u2013267 (2010).","journal-title":"J. Immunol."},{"key":"15844_CR36","doi-asserted-by":"publisher","first-page":"e1005415","DOI":"10.1371\/journal.ppat.1005415","volume":"12","author":"Y Zheng","year":"2016","unstructured":"Zheng, Y., Stamminger, T. & Hearing, P. E2F\/Rb family proteins mediate interferon induced repression of adenovirus immediate early transcription to promote persistent viral infection. PLoS Pathog. 12, e1005415 (2016).","journal-title":"PLoS Pathog."},{"key":"15844_CR37","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1101\/gad.839400","volume":"14","author":"W Tirasophon","year":"2000","unstructured":"Tirasophon, W., Lee, K., Callaghan, B., Welihinda, A. & Kaufman, R. J. The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response. Genes Dev. 14, 2725\u20132736 (2000).","journal-title":"Genes Dev."},{"key":"15844_CR38","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.semcdb.2007.09.003","volume":"18","author":"JD Malhotra","year":"2007","unstructured":"Malhotra, J. D. & Kaufman, R. J. The endoplasmic reticulum and the unfolded protein response. Semin. Cell Dev. Biol. 18, 716\u2013731 (2007).","journal-title":"Semin. Cell Dev. Biol."},{"key":"15844_CR39","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.chom.2013.09.004","volume":"14","author":"IH Wang","year":"2013","unstructured":"Wang, I. H. et al. Tracking viral genomes in host cells at single-molecule resolution. Cell Host Microbe 14, 468\u2013480 (2013).","journal-title":"Cell Host Microbe"},{"key":"15844_CR40","doi-asserted-by":"publisher","first-page":"E869","DOI":"10.1073\/pnas.1115623109","volume":"109","author":"BC Cross","year":"2012","unstructured":"Cross, B. C. et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc. Natl Acad. Sci. USA 109, E869\u2013E878 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR41","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.cell.2009.07.017","volume":"138","author":"D Han","year":"2009","unstructured":"Han, D. et al. IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138, 562\u2013575 (2009).","journal-title":"Cell"},{"key":"15844_CR42","doi-asserted-by":"publisher","first-page":"7836","DOI":"10.1038\/sj.onc.1204861","volume":"20","author":"E White","year":"2001","unstructured":"White, E. Regulation of the cell cycle and apoptosis by the oncogenes of adenovirus. Oncogene 20, 7836\u20137846 (2001).","journal-title":"Oncogene"},{"key":"15844_CR43","doi-asserted-by":"publisher","first-page":"4628","DOI":"10.1073\/pnas.1217611110","volume":"110","author":"R Volmer","year":"2013","unstructured":"Volmer, R., van der Ploeg, K. & Ron, D. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl Acad. Sci. USA 110, 4628\u20134633 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR44","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/BF01964706","volume":"29","author":"O Thastrup","year":"1990","unstructured":"Thastrup, O. Role of Ca2(+)-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2(+)-ATPase inhibitor, thapsigargin. Agents Actions 29, 8\u201315 (1990).","journal-title":"Agents Actions"},{"key":"15844_CR45","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/S1097-2765(00)80330-5","volume":"5","author":"HP Harding","year":"2000","unstructured":"Harding, H. P., Zhang, Y., Bertolotti, A., Zeng, H. & Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5, 897\u2013904 (2000).","journal-title":"Mol. Cell"},{"key":"15844_CR46","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/35014014","volume":"2","author":"A Bertolotti","year":"2000","unstructured":"Bertolotti, A., Zhang, Y., Hendershot, L. M., Harding, H. P. & Ron, D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2, 326\u2013332 (2000).","journal-title":"Nat. Cell Biol."},{"key":"15844_CR47","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1016\/j.cell.2017.10.040","volume":"171","author":"N Amin-Wetzel","year":"2017","unstructured":"Amin-Wetzel, N. et al. A J-protein co-chaperone recruits BiP to monomerize IRE1 and repress the unfolded protein response. Cell 171, 1625\u20131637 (2017). e1613.","journal-title":"Cell"},{"key":"15844_CR48","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/0092-8674(84)90045-X","volume":"36","author":"C Montell","year":"1984","unstructured":"Montell, C., Courtois, G., Eng, C. & Berk, A. Complete transformation by adenovirus 2 requires both E1A proteins. Cell 36, 951\u2013961 (1984).","journal-title":"Cell"},{"key":"15844_CR49","first-page":"163","volume":"273","author":"C Endter","year":"2004","unstructured":"Endter, C. & Dobner, T. Cell transformation by human adenoviruses. Curr. Top. Microbiol. Immunol. 273, 163\u2013214 (2004).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"15844_CR50","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1128\/AAC.6.5.598","volume":"6","author":"CB Lauter","year":"1974","unstructured":"Lauter, C. B., Bailey, E. J. & Lerner, A. M. Assessment of cytosine arabinoside as an antiviral agent in humans. Antimicrob. Agents Chemother. 6, 598\u2013602 (1974).","journal-title":"Antimicrob. Agents Chemother."},{"key":"15844_CR51","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1158\/0008-5472.CAN-05-1484","volume":"66","author":"M Schumann","year":"2006","unstructured":"Schumann, M. & Dobbelstein, M. Adenovirus-induced extracellular signal-regulated kinase phosphorylation during the late phase of infection enhances viral protein levels and virus progeny. Cancer Res. 66, 1282\u20131288 (2006).","journal-title":"Cancer Res."},{"key":"15844_CR52","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1021\/acsinfecdis.7b00009","volume":"3","author":"V Prasad","year":"2017","unstructured":"Prasad, V., Suomalainen, M., Hemmi, S. & Greber, U. F. Cell cycle-dependent kinase Cdk9 is a postexposure drug target against human adenoviruses. ACS Infect. Dis. 3, 398\u2013405 (2017).","journal-title":"ACS Infect. Dis."},{"key":"15844_CR53","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/0092-8674(82)90310-5","volume":"31","author":"B Thimmappaya","year":"1982","unstructured":"Thimmappaya, B., Weinberger, C., Schneider, R. J. & Shenk, T. Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell 31, 543\u2013551 (1982).","journal-title":"Cell"},{"key":"15844_CR54","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/0092-8674(79)90275-7","volume":"17","author":"N Jones","year":"1979","unstructured":"Jones, N. & Shenk, T. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17, 683\u2013689 (1979).","journal-title":"Cell"},{"key":"15844_CR55","doi-asserted-by":"publisher","first-page":"10123","DOI":"10.1128\/JVI.01102-12","volume":"86","author":"A Yakimovich","year":"2012","unstructured":"Yakimovich, A. et al. Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model. J. Virol. 86, 10123\u201310137 (2012).","journal-title":"J. Virol."},{"key":"15844_CR56","doi-asserted-by":"publisher","first-page":"6104","DOI":"10.1128\/JVI.03391-12","volume":"87","author":"M Sester","year":"2013","unstructured":"Sester, M., Ruszics, Z., Mackley, E. & Burgert, H. G. The transmembrane domain of the adenovirus E3\/19K protein acts as an endoplasmic reticulum retention signal and contributes to intracellular sequestration of major histocompatibility complex class I molecules. J. Virol. 87, 6104\u20136117 (2013).","journal-title":"J. Virol."},{"key":"15844_CR57","doi-asserted-by":"publisher","first-page":"9900","DOI":"10.1073\/pnas.1701757114","volume":"114","author":"N Blazanin","year":"2017","unstructured":"Blazanin, N. et al. ER stress and distinct outputs of the IRE1alpha RNase control proliferation and senescence in response to oncogenic Ras. Proc. Natl Acad. Sci. USA 114, 9900\u20139905 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR58","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1128\/MCB.00136-15","volume":"35","author":"D Hasegawa","year":"2015","unstructured":"Hasegawa, D. et al. Epithelial Xbp1 is required for cellular proliferation and differentiation during mammary gland development. Mol. Cell Biol. 35, 1543\u20131556 (2015).","journal-title":"Mol. Cell Biol."},{"key":"15844_CR59","doi-asserted-by":"publisher","first-page":"13086","DOI":"10.1128\/JVI.02156-14","volume":"88","author":"V Prasad","year":"2014","unstructured":"Prasad, V. et al. Chemical induction of unfolded protein response enhances cancer cell killing through lytic virus infection. J. Virol. 88, 13086\u201313098 (2014).","journal-title":"J. Virol."},{"key":"15844_CR60","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.molcel.2007.06.011","volume":"27","author":"D Acosta-Alvear","year":"2007","unstructured":"Acosta-Alvear, D. et al. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol. Cell 27, 53\u201366 (2007).","journal-title":"Mol. Cell"},{"key":"15844_CR61","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature13119","volume":"508","author":"X Chen","year":"2014","unstructured":"Chen, X. et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway. Nature 508, 103\u2013107 (2014).","journal-title":"Nature"},{"key":"15844_CR62","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1126\/science.1209235","volume":"334","author":"MH Smith","year":"2011","unstructured":"Smith, M. H., Ploegh, H. L. & Weissman, J. S. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science 334, 1086\u20131090 (2011).","journal-title":"Science"},{"key":"15844_CR63","doi-asserted-by":"publisher","first-page":"e0204522","DOI":"10.1371\/journal.pone.0204522","volume":"13","author":"A Valdes","year":"2018","unstructured":"Valdes, A., Zhao, H., Pettersson, U. & Lind, S. B. Time-resolved proteomics of adenovirus infected cells. PLoS ONE 13, e0204522 (2018).","journal-title":"PLoS ONE"},{"key":"15844_CR64","doi-asserted-by":"publisher","first-page":"e43036","DOI":"10.7554\/eLife.43036","volume":"7","author":"D Acosta-Alvear","year":"2018","unstructured":"Acosta-Alvear, D, et al. The unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1. Elife 7, e43036 (2018).","journal-title":"Elife"},{"key":"15844_CR65","doi-asserted-by":"publisher","first-page":"e30700","DOI":"10.7554\/eLife.30700","volume":"6","author":"GE Karagoz","year":"2017","unstructured":"Karagoz, G.E., et al. An unfolded protein-induced conformational switch activates mammalian IRE1. Elife 6, e30700 (2017).","journal-title":"Elife"},{"key":"15844_CR66","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.virol.2009.02.021","volume":"387","author":"SC Sung","year":"2009","unstructured":"Sung, S. C., Chao, C. Y., Jeng, K. S., Yang, J. Y. & Lai, M. M. The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6. Virology 387, 402\u2013413 (2009).","journal-title":"Virology"},{"key":"15844_CR67","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.molcel.2017.06.012","volume":"67","author":"K Halbleib","year":"2017","unstructured":"Halbleib, K. et al. Activation of the unfolded protein response by lipid bilayer stress. Mol. Cell 67, 673\u2013684 (2017). e678.","journal-title":"Mol. Cell"},{"key":"15844_CR68","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrm2199","volume":"8","author":"D Ron","year":"2007","unstructured":"Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519\u2013529 (2007).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"15844_CR69","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.virol.2018.03.006","volume":"518","author":"B Meltzer","year":"2018","unstructured":"Meltzer, B. et al. Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages. Virology 518, 241\u2013252 (2018).","journal-title":"Virology"},{"key":"15844_CR70","doi-asserted-by":"publisher","first-page":"8182","DOI":"10.1128\/JVI.00712-09","volume":"83","author":"AR Cliffe","year":"2009","unstructured":"Cliffe, A. R., Garber, D. A. & Knipe, D. M. Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J. Virol. 83, 8182\u20138190 (2009).","journal-title":"J. Virol."},{"key":"15844_CR71","doi-asserted-by":"publisher","first-page":"4435","DOI":"10.1002\/j.1460-2075.1990.tb07894.x","volume":"9","author":"JL Williams","year":"1990","unstructured":"Williams, J. L. et al. Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs. EMBO J. 9, 4435\u20134442 (1990).","journal-title":"EMBO J."},{"key":"15844_CR72","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1128\/MCB.26.8.3071-3084.2006","volume":"26","author":"P Hu","year":"2006","unstructured":"Hu, P., Han, Z., Couvillon, A. D., Kaufman, R. J. & Exton, J. H. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell Biol. 26, 3071\u20133084 (2006).","journal-title":"Mol. Cell Biol."},{"key":"15844_CR73","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/cgt.2009.12","volume":"16","author":"S Bortolanza","year":"2009","unstructured":"Bortolanza, S. et al. Deletion of the E3-6.7K\/gp19K region reduces the persistence of wild-type adenovirus in a permissive tumor model in Syrian hamsters. Cancer Gene Ther. 16, 703\u2013712 (2009).","journal-title":"Cancer Gene Ther."},{"key":"15844_CR74","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41593-017-0038-4","volume":"21","author":"I Gladwyn-Ng","year":"2018","unstructured":"Gladwyn-Ng, I. et al. Stress-induced unfolded protein response contributes to Zika virus-associated microcephaly. Nat. Neurosci. 21, 63\u201371 (2018).","journal-title":"Nat. Neurosci."},{"key":"15844_CR75","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1006\/viro.2001.1204","volume":"290","author":"J Yu","year":"2001","unstructured":"Yu, J., Boyapati, A. & Rundell, K. Critical role for SV40 small-t antigen in human cell transformation. Virology 290, 192\u2013198 (2001).","journal-title":"Virology"},{"key":"15844_CR76","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.virol.2005.08.024","volume":"343","author":"D Sirena","year":"2005","unstructured":"Sirena, D., Ruzsics, Z., Schaffner, W., Greber, U. F. & Hemmi, S. The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3. Virology 343, 283\u2013298 (2005).","journal-title":"Virology"},{"key":"15844_CR77","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1093\/nar\/gni035","volume":"33","author":"S Warming","year":"2005","unstructured":"Warming, S., Costantino, N., Court, D. L., Jenkins, N. A. & Copeland, N. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res. 33, e36 (2005).","journal-title":"Nucleic Acids Res."},{"key":"15844_CR78","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/0092-8674(83)90012-0","volume":"33","author":"P Hearing","year":"1983","unstructured":"Hearing, P. & Shenk, T. The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell 33, 695\u2013703 (1983).","journal-title":"Cell"},{"key":"15844_CR79","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1247005","volume":"343","author":"O Shalem","year":"2014","unstructured":"Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84\u201387 (2014).","journal-title":"Science"},{"key":"15844_CR80","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nature12064","volume":"500","author":"A Adey","year":"2013","unstructured":"Adey, A. et al. The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line. Nature 500, 207\u2013211 (2013).","journal-title":"Nature"},{"key":"15844_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04379-2","volume":"9","author":"M Crameri","year":"2018","unstructured":"Crameri, M. et al. MxB is an interferon-induced restriction factor of human herpesviruses. Nat. Commun. 9, 1980 (2018).","journal-title":"Nat. Commun."},{"key":"15844_CR82","doi-asserted-by":"publisher","first-page":"E4884","DOI":"10.1073\/pnas.1312420110","volume":"110","author":"M Windheim","year":"2013","unstructured":"Windheim, M. et al. A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions. Proc. Natl Acad. Sci. USA 110, E4884\u2013E4893 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"15844_CR83","doi-asserted-by":"publisher","first-page":"8049","DOI":"10.1093\/nar\/gku480","volume":"42","author":"M Hannus","year":"2014","unstructured":"Hannus, M. et al. siPools: highly complex but accurately defined siRNA pools eliminate off-target effects. Nucleic Acids Res. 42, 8049\u20138061 (2014).","journal-title":"Nucleic Acids Res."},{"key":"15844_CR84","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.molimm.2008.06.019","volume":"46","author":"B Menz","year":"2008","unstructured":"Menz, B., Sester, M., Koebernick, K., Schmid, R. & Burgert, H. G. Structural analysis of the adenovirus type 2 E3\/19K protein using mutagenesis and a panel of conformation-sensitive monoclonal antibodies. Mol. Immunol. 46, 16\u201326 (2008).","journal-title":"Mol. Immunol."},{"key":"15844_CR85","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1021\/ja046699g","volume":"127","author":"TJ Magliery","year":"2005","unstructured":"Magliery, T. J. et al. Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism. J. Am. Chem. Soc. 127, 146\u2013157 (2005).","journal-title":"J. Am. Chem. Soc."},{"key":"15844_CR86","doi-asserted-by":"publisher","DOI":"10.1038\/srep02854","volume":"3","author":"S Cabantous","year":"2013","unstructured":"Cabantous, S. et al. A new protein-protein interaction sensor based on tripartite split-GFP association. Sci. Rep. 3, 2854 (2013).","journal-title":"Sci. Rep."},{"key":"15844_CR87","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r100","volume":"7","author":"AE Carpenter","year":"2006","unstructured":"Carpenter, A. E. et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 7, R100 (2006).","journal-title":"Genome Biol."},{"key":"15844_CR88","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"MW Pfaffl","year":"2001","unstructured":"Pfaffl, M. W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45 (2001).","journal-title":"Nucleic Acids Res."},{"key":"15844_CR89","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1093\/bioinformatics\/15.7.622","volume":"15","author":"T Tsunoda","year":"1999","unstructured":"Tsunoda, T. & Takagi, T. Estimating transcription factor bindability on DNA. Bioinformatics 15, 622\u2013630 (1999).","journal-title":"Bioinformatics"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-15844-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-15844-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-15844-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T20:59:58Z","timestamp":1670273998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-15844-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["15844"],"URL":"https:\/\/doi.org\/10.1038\/s41467-020-15844-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]},"assertion":[{"value":"14 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2020","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":"1997"}}