{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:04:25Z","timestamp":1767179065416,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010588","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000}}],"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY013124"],"award-info":[{"award-number":["EY013124"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY021558"],"award-info":[{"award-number":["EY021558"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY021558"],"award-info":[{"award-number":["EY021558"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY013124"],"award-info":[{"award-number":["EY013124"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY014104"],"award-info":[{"award-number":["EY014104"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness, Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001610","name":"Falk Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001610","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Agencia Estatal de Investigaci\u00f3n and European Regional Development Fund","award":["PID2019-104098GB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-104098GB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"CNB-CSIC Severo Ochoa Excellence","award":["SEV 2017-0712"],"award-info":[{"award-number":["SEV 2017-0712"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus outbreaks are associated with severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy available. An adenoviral vaccine based on human adenovirus species D (HAdV-D) is currently in use for COVID-19. Herein, we investigate host interactions of HAdV-D type 37 (HAdV-D37) protein IIIa (pIIIa), identified by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2). USP9x binding did not invoke its signature deubiquitination function but rather deregulated pIIIa-RANBP2 interactions. In USP9x-knockout cells, viral genome replication and viral protein expression increased compared to wild type cells, supporting a host-favored mechanism for USP9x. Conversely, RANBP2-knock down reduced pIIIa transport to the nucleus, viral genome replication, and viral protein expression. Also, RANBP2-siRNA pretreated cells appeared to contain fewer mature viral particles. Transmission electron microscopy of USP9x-siRNA pretreated, virus-infected cells revealed larger than typical paracrystalline viral arrays. RANBP2-siRNA pretreatment led to the accumulation of defective assembly products at an early maturation stage. CRM1 nuclear export blockade by leptomycin B led to the retention of pIIIa within cell nuclei and hindered pIIIa-RANBP2 interactions.\n                    <jats:italic>In-vitro<\/jats:italic>\n                    binding analyses indicated that USP9x and RANBP2 bind to C-terminus of pIIIa amino acids 386\u2013563 and 386\u2013510, respectively. Surface plasmon resonance testing showed direct pIIIa interaction with recombinant USP9x and RANBP2 proteins, without competition. Using an alternative and genetically disparate adenovirus type (HAdV-C5), we show that the demonstrated pIIIa interaction is also important for a severe respiratory pathogen. Together, our results suggest that pIIIa hijacks RANBP2 for nuclear import and subsequent virion assembly. USP9x counteracts this interaction and negatively regulates virion synthesis. This analysis extends the scope of known adenovirus-host interactions and has potential implications in designing new antiviral therapeutics.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010588","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T13:54:56Z","timestamp":1655387696000},"page":"e1010588","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["RANBP2 and USP9x regulate nuclear import of adenovirus minor coat protein IIIa"],"prefix":"10.1371","volume":"18","author":[{"given":"Ashrafali M.","family":"Ismail","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrita","family":"Saha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-0448","authenticated-orcid":true,"given":"David F.","family":"Painter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-0456","authenticated-orcid":true,"given":"Gurdeep","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela N.","family":"Condezo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Chodosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"San Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-5613","authenticated-orcid":true,"given":"Jaya","family":"Rajaiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ppat.1010588.ref001","article-title":"Proteomic and interactomic insights into the molecular basis of cell functional diversity","author":"I Bludau","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"ppat.1010588.ref002","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/s41467-020-14586-5","article-title":"Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection","volume":"11","author":"Y Hashimoto","year":"2020","journal-title":"Nat Commun."},{"issue":"6","key":"ppat.1010588.ref003","doi-asserted-by":"crossref","first-page":"e3000316","DOI":"10.1371\/journal.pbio.3000316","article-title":"Protein interactions and consensus clustering analysis uncover insights into herpesvirus virion structure and function relationships","volume":"17","author":"A Hernandez Duran","year":"2019","journal-title":"PLoS Biol"},{"key":"ppat.1010588.ref004","doi-asserted-by":"crossref","first-page":"11473","DOI":"10.1038\/ncomms11473","article-title":"The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation","volume":"7","author":"N Martinez-Martin","year":"2016","journal-title":"Nat Commun"},{"issue":"3","key":"ppat.1010588.ref005","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1586\/14789450.2016.1147353","article-title":"Proteomic approaches to uncovering virus-host protein interactions during the progression of viral infection","volume":"13","author":"KK Lum","year":"2016","journal-title":"Expert Rev Proteomics"},{"issue":"D1","key":"ppat.1010588.ref006","first-page":"D1145","article-title":"The ProteomeXchange consortium in 2020: enabling \u2019big data\u2019 approaches in proteomics","volume":"48","author":"EW Deutsch","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010588.ref007","article-title":"A systems approach to infectious disease","author":"M Eckhardt","year":"2020","journal-title":"Nat Rev Genet"},{"issue":"24","key":"ppat.1010588.ref008","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1002\/1873-3468.13693","article-title":"Genomic foundations of evolution and ocular pathogenesis in human adenovirus species D","volume":"593","author":"AM Ismail","year":"2019","journal-title":"FEBS Lett"},{"issue":"2","key":"ppat.1010588.ref009","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1128\/jvi.16.2.366-387.1975","article-title":"Structure and composition of the adenovirus type 2 core","volume":"16","author":"DT Brown","year":"1975","journal-title":"J Virol"},{"issue":"4754","key":"ppat.1010588.ref010","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1126\/science.3704642","article-title":"Three-dimensional structure of the adenovirus major coat protein hexon","volume":"232","author":"MM Roberts","year":"1986","journal-title":"Science"},{"issue":"6756","key":"ppat.1010588.ref011","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/44880","article-title":"A triple beta-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein","volume":"401","author":"MJ van Raaij","year":"1999","journal-title":"Nature"},{"issue":"1","key":"ppat.1010588.ref012","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.molcel.2004.11.041","article-title":"The structure of the human adenovirus 2 penton","volume":"17","author":"C Zubieta","year":"2005","journal-title":"Mol Cell"},{"issue":"24","key":"ppat.1010588.ref013","doi-asserted-by":"crossref","first-page":"12049","DOI":"10.1128\/JVI.01652-06","article-title":"Visualization of alpha-helices in a 6-angstrom resolution cryoelectron microscopy structure of adenovirus allows refinement of capsid protein assignments","volume":"80","author":"SD Saban","year":"2006","journal-title":"J Virol"},{"issue":"2","key":"ppat.1010588.ref014","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1128\/jvi.55.2.379-386.1985","article-title":"Interactions among the three adenovirus core proteins","volume":"55","author":"PK Chatterjee","year":"1985","journal-title":"J Virol"},{"issue":"21","key":"ppat.1010588.ref015","doi-asserted-by":"crossref","first-page":"10446","DOI":"10.1128\/JVI.75.21.10446-10454.2001","article-title":"Role for the adenovirus IVa2 protein in packaging of viral DNA","volume":"75","author":"W Zhang","year":"2001","journal-title":"J Virol"},{"issue":"10","key":"ppat.1010588.ref016","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1093\/nar\/21.10.2293","article-title":"The adenovirus terminal protein influences binding of replication proteins and changes the origin structure","volume":"21","author":"R Pronk","year":"1993","journal-title":"Nucleic Acids Res"},{"issue":"41","key":"ppat.1010588.ref017","doi-asserted-by":"crossref","first-page":"12349","DOI":"10.1021\/bi0109008","article-title":"Interaction of the human adenovirus proteinase with its 11-amino acid cofactor pVIc","volume":"40","author":"ML Baniecki","year":"2001","journal-title":"Biochemistry"},{"issue":"5","key":"ppat.1010588.ref018","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3390\/v4050847","article-title":"Latest insights on adenovirus structure and assembly","volume":"4","author":"C. San Martin","year":"2012","journal-title":"Viruses"},{"issue":"23","key":"ppat.1010588.ref019","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1093\/emboj\/cdg614","article-title":"Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals","volume":"22","author":"H Wodrich","year":"2003","journal-title":"EMBO J"},{"issue":"4","key":"ppat.1010588.ref020","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1128\/JVI.79.4.1992-2000.2005","article-title":"Adenovirus protein VI mediates membrane disruption following capsid disassembly","volume":"79","author":"CM Wiethoff","year":"2005","journal-title":"J Virol"},{"issue":"6","key":"ppat.1010588.ref021","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1128\/JVI.02321-10","article-title":"Functional genetic and biophysical analyses of membrane disruption by human adenovirus","volume":"85","author":"CL Moyer","year":"2011","journal-title":"J Virol"},{"issue":"7013","key":"ppat.1010588.ref022","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature03056","article-title":"Insights into assembly from structural analysis of bacteriophage PRD1","volume":"432","author":"NG Abrescia","year":"2004","journal-title":"Nature"},{"issue":"1","key":"ppat.1010588.ref023","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/jcb.20523","article-title":"Control of adenovirus packaging","volume":"96","author":"P Ostapchuk","year":"2005","journal-title":"J Cell Biochem"},{"issue":"4","key":"ppat.1010588.ref024","doi-asserted-by":"crossref","first-page":"e1006320","DOI":"10.1371\/journal.ppat.1006320","article-title":"Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center","volume":"13","author":"GN Condezo","year":"2017","journal-title":"PLoS Pathog."},{"issue":"8","key":"ppat.1010588.ref025","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1128\/jvi.61.8.2555-2558.1987","article-title":"Identification of a repeated sequence element required for efficient encapsidation of the adenovirus type 5 chromosome","volume":"61","author":"P Hearing","year":"1987","journal-title":"J Virol"},{"issue":"2","key":"ppat.1010588.ref026","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/jvi.26.2.344-356.1978","article-title":"Temperature-sensitive mutant of adenovirus type 2 blocked in virion assembly: accumulation of light intermediate particles","volume":"26","author":"JC D\u2019Halluin","year":"1978","journal-title":"J Virol"},{"key":"ppat.1010588.ref027","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.virol.2014.05.030","article-title":"IIIa deleted adenovirus as a single-cycle genome replicating vector","volume":"462\u2013463","author":"CM Crosby","year":"2014","journal-title":"Virology"},{"issue":"3","key":"ppat.1010588.ref028","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/nar\/22.3.332","article-title":"Regulation of adenovirus alternative RNA splicing at the level of commitment complex formation","volume":"22","author":"JP Kreivi","year":"1994","journal-title":"Nucleic Acids Res"},{"issue":"5822","key":"ppat.1010588.ref029","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/292420a0","article-title":"Controls of RNA splicing and termination in the major late adenovirus transcription unit","volume":"292","author":"G Akusjarvi","year":"1981","journal-title":"Nature"},{"issue":"13","key":"ppat.1010588.ref030","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1073\/pnas.83.13.4690","article-title":"Defective RNA splicing in the absence of adenovirus-associated RNAI","volume":"83","author":"C Svensson","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"ppat.1010588.ref031","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.1128\/JVI.00467-11","article-title":"Adenovirus structural protein IIIa is involved in the serotype specificity of viral DNA packaging","volume":"85","author":"HC Ma","year":"2011","journal-title":"J Virol"},{"issue":"4","key":"ppat.1010588.ref032","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.jmb.2008.08.054","article-title":"Localization of the N-terminus of minor coat protein IIIa in the adenovirus capsid","volume":"383","author":"C San Martin","year":"2008","journal-title":"J Mol Biol"},{"issue":"5","key":"ppat.1010588.ref033","doi-asserted-by":"crossref","first-page":"e1602670","DOI":"10.1126\/sciadv.1602670","article-title":"Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses.","volume":"3","author":"X Yu","year":"2017","journal-title":"Sci Adv."},{"issue":"5995","key":"ppat.1010588.ref034","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1126\/science.1187433","article-title":"Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks","volume":"329","author":"H Liu","year":"2010","journal-title":"Science"},{"issue":"8","key":"ppat.1010588.ref035","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.3390\/v5082019","article-title":"Viral subversion of the nuclear pore complex.","volume":"5","author":"V Le Sage","year":"2013","journal-title":"Viruses"},{"issue":"6","key":"ppat.1010588.ref036","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1128\/jvi.70.6.3449-3460.1996","article-title":"Nucleoplasmic and nucleolar distribution of the adenovirus IVa2 gene product","volume":"70","author":"P Lutz","year":"1996","journal-title":"J Virol"},{"issue":"24","key":"ppat.1010588.ref037","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1002\/1873-3468.13672","article-title":"Formation of adenovirus DNA replication compartments","volume":"593","author":"P Hidalgo","year":"2019","journal-title":"FEBS Lett"},{"issue":"1","key":"ppat.1010588.ref038","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajpath.2010.11.030","article-title":"Regulation of AMPK by the ubiquitin proteasome system","volume":"178","author":"M Zungu","year":"2011","journal-title":"The American journal of pathology"},{"issue":"10","key":"ppat.1010588.ref039","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.3390\/v5102483","article-title":"Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes","volume":"5","author":"KA Matreyek","year":"2013","journal-title":"Viruses"},{"key":"ppat.1010588.ref040","doi-asserted-by":"crossref","first-page":"11482","DOI":"10.1038\/ncomms11482","article-title":"The RanBP2\/RanGAP1*SUMO1\/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes","volume":"7","author":"T Ritterhoff","year":"2016","journal-title":"Nat Commun."},{"issue":"2","key":"ppat.1010588.ref041","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF01553491","article-title":"Compartmentalization of cellular and viral DNAs in adenovirus type 5 infection as revealed by ultrastructural in situ hybridization","volume":"2","author":"S Besse","year":"1994","journal-title":"Chromosome Res"},{"issue":"1","key":"ppat.1010588.ref042","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0092-8674(77)90202-1","article-title":"Viral DNA sequences from incomplete particles of human adenovirus type 7","volume":"12","author":"C. Tibbetts","year":"1977","journal-title":"Cell"},{"issue":"15","key":"ppat.1010588.ref043","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1089\/104303401753153974","article-title":"Empty capsids in column-purified recombinant adenovirus preparations","volume":"12","author":"G Vellekamp","year":"2001","journal-title":"Hum Gene Ther"},{"issue":"3","key":"ppat.1010588.ref044","doi-asserted-by":"crossref","first-page":"e1004696","DOI":"10.1371\/journal.ppat.1004696","article-title":"Adenovirus entry from the apical surface of polarized epithelia is facilitated by the host innate immune response.","volume":"11","author":"PL Kotha","year":"2015","journal-title":"PLoS pathogens."},{"issue":"3","key":"ppat.1010588.ref045","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.molcel.2005.12.011","article-title":"Mapping pathways and phenotypes by systematic gene overexpression","volume":"21","author":"R Sopko","year":"2006","journal-title":"Mol Cell"},{"issue":"1","key":"ppat.1010588.ref046","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.cell.2009.04.029","article-title":"Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity","volume":"138","author":"T Vavouri","year":"2009","journal-title":"Cell"},{"issue":"22","key":"ppat.1010588.ref047","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1091\/mbc.E15-07-0512","article-title":"Quantitative nature of overexpression experiments","volume":"26","author":"H. Moriya","year":"2015","journal-title":"Mol Biol Cell"},{"key":"ppat.1010588.ref048","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-9232-4_9","article-title":"Considerations for Identifying Endogenous Protein Complexes from Tissue via Immunoaffinity Purification and Quantitative Mass Spectrometry.","volume":"1977","author":"JD Federspiel","year":"2019","journal-title":"Methods Mol Biol"},{"issue":"1","key":"ppat.1010588.ref049","first-page":"5","article-title":"The ubiquitin-proteasome pathway in viral infections","volume":"84","author":"G Gao","year":"2006","journal-title":"Can J Physiol Pharmacol"},{"issue":"3","key":"ppat.1010588.ref050","doi-asserted-by":"crossref","first-page":"e1005022","DOI":"10.1371\/journal.pgen.1005022","article-title":"Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase","volume":"11","author":"L Paemka","year":"2015","journal-title":"PLoS Genet."},{"issue":"9","key":"ppat.1010588.ref051","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/emboj.2010.46","article-title":"USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly","volume":"29","author":"D Theard","year":"2010","journal-title":"EMBO J"},{"issue":"21","key":"ppat.1010588.ref052","doi-asserted-by":"crossref","first-page":"10477","DOI":"10.1128\/JVI.01113-08","article-title":"Epstein-barr virus encodes three bona fide ubiquitin-specific proteases","volume":"82","author":"R Sompallae","year":"2008","journal-title":"J Virol"},{"issue":"4","key":"ppat.1010588.ref053","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.molcel.2005.07.003","article-title":"A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine proteases that is conserved across the family Herpesviridae","volume":"19","author":"LM Kattenhorn","year":"2005","journal-title":"Mol 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Microbe"},{"issue":"9","key":"ppat.1010588.ref057","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/12478","article-title":"Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells","volume":"5","author":"R Tomazin","year":"1999","journal-title":"Nat Med"},{"issue":"6608","key":"ppat.1010588.ref058","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/384432a0","article-title":"Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction","volume":"384","author":"EJ Wiertz","year":"1996","journal-title":"Nature"},{"issue":"5","key":"ppat.1010588.ref059","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0092-8674(00)81054-5","article-title":"The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol","volume":"84","author":"EJ Wiertz","year":"1996","journal-title":"Cell"},{"issue":"8","key":"ppat.1010588.ref060","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1073\/pnas.0308411100","article-title":"Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells","volume":"101","author":"H Ovaa","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"ppat.1010588.ref061","doi-asserted-by":"crossref","first-page":"6323","DOI":"10.1128\/JVI.76.12.6323-6331.2002","article-title":"Deubiquitinating function of adenovirus proteinase","volume":"76","author":"MY Balakirev","year":"2002","journal-title":"J Virol"},{"issue":"7","key":"ppat.1010588.ref062","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1083\/jcb.200111010","article-title":"A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition","volume":"155","author":"L Coscoy","year":"2001","journal-title":"The Journal of cell biology"},{"issue":"8","key":"ppat.1010588.ref063","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1038\/sj.emboj.7601056","article-title":"Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules","volume":"25","author":"LM Duncan","year":"2006","journal-title":"EMBO J"},{"issue":"4","key":"ppat.1010588.ref064","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1128\/JVI.02257-14","article-title":"The amphipathic helix of adenovirus capsid protein VI contributes to penton release and postentry sorting","volume":"89","author":"R Martinez","year":"2015","journal-title":"J Virol"},{"issue":"2","key":"ppat.1010588.ref065","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.virol.2012.05.028","article-title":"Adenoviral protein V promotes a process of viral assembly through nucleophosmin 1","volume":"432","author":"H Ugai","year":"2012","journal-title":"Virology"},{"issue":"4","key":"ppat.1010588.ref066","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1128\/MMBR.65.4.570-594.2001","article-title":"Transport into and out of the nucleus","volume":"65","author":"IG Macara","year":"2001","journal-title":"Microbiol Mol Biol Rev"},{"issue":"1","key":"ppat.1010588.ref067","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.molcel.2010.01.040","article-title":"Gene regulation by nucleoporins and links to cancer","volume":"38","author":"A Kohler","year":"2010","journal-title":"Mol Cell"},{"issue":"4","key":"ppat.1010588.ref068","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1083\/jcb.201102018","article-title":"Ran-dependent docking of importin-beta to RanBP2\/Nup358 filaments is essential for protein import and cell viability","volume":"194","author":"M Hamada","year":"2011","journal-title":"The Journal of cell 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Engelsma","year":"2004","journal-title":"EMBO J"},{"issue":"3","key":"ppat.1010588.ref072","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1073\/pnas.1215214110","article-title":"Structural basis for cooperativity of CRM1 export complex formation","volume":"110","author":"T Monecke","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Pt 11","key":"ppat.1010588.ref073","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1242\/jcs.01076","article-title":"CRM1-dependent, but not ARE-mediated, nuclear export of IFN-alpha1 mRNA","volume":"117","author":"T Kimura","year":"2004","journal-title":"J Cell Sci"},{"issue":"4","key":"ppat.1010588.ref074","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1128\/JVI.06275-11","article-title":"CRM1-dependent transport supports cytoplasmic accumulation of adenoviral early transcripts","volume":"86","author":"M Schmid","year":"2012","journal-title":"J Virol"},{"issue":"4","key":"ppat.1010588.ref075","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.tcb.2007.02.003","article-title":"CRM1-mediated nuclear export: to the pore and beyond","volume":"17","author":"S Hutten","year":"2007","journal-title":"Trends Cell Biol"},{"issue":"9","key":"ppat.1010588.ref076","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1128\/JVI.78.9.4389-4396.2004","article-title":"Viral regulation of mRNA export","volume":"78","author":"RM Sandri-Goldin","year":"2004","journal-title":"J Virol"},{"issue":"2","key":"ppat.1010588.ref077","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1128\/jvi.19.2.643-658.1976","article-title":"Characterization of a temperature-sensitive, hexon transport mutant of type 5 adenovirus","volume":"19","author":"RS Kauffman","year":"1976","journal-title":"J Virol"},{"issue":"19","key":"ppat.1010588.ref078","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1093\/emboj\/16.19.5998","article-title":"The role of the nuclear pore complex in adenovirus DNA entry","volume":"16","author":"UF Greber","year":"1997","journal-title":"EMBO J"},{"issue":"2","key":"ppat.1010588.ref079","first-page":"379","article-title":"Replicating single-stranded adenovirus type 5 DNA molecules accumulate within well-delimited intranuclear areas of lytically infected HeLa cells","volume":"52","author":"F Puvion-Dutilleul","year":"1990","journal-title":"Eur J Cell Biol"},{"issue":"1","key":"ppat.1010588.ref080","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0042-6822(90)90202-3","article-title":"Purification and characterization of wild-type and ts 112 mutant protein IIIa of human adenovirus 2 expressed in Escherichia coli","volume":"175","author":"M Cuillel","year":"1990","journal-title":"Virology"},{"issue":"3","key":"ppat.1010588.ref081","first-page":"745","article-title":"Structural proteins of adenoviruses. 8. Characterization of incomplete particles of adenovirus type 3","volume":"49","author":"L Prage","year":"1972","journal-title":"Virology"},{"issue":"5","key":"ppat.1010588.ref082","doi-asserted-by":"crossref","first-page":"e19564","DOI":"10.1371\/journal.pone.0019564","article-title":"Altering the Ad5 packaging domain affects the maturation of the Ad particles","volume":"6","author":"R Alba","year":"2011","journal-title":"PLoS One."},{"issue":"18","key":"ppat.1010588.ref083","doi-asserted-by":"crossref","first-page":"9653","DOI":"10.1128\/JVI.01453-15","article-title":"Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52\/55k","volume":"89","author":"GN Condezo","year":"2015","journal-title":"J Virol"},{"issue":"3","key":"ppat.1010588.ref084","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1292\/jvms.15-0598","article-title":"Ubiquitin-specific protease 9X in host cells interacts with herpes simplex virus 1 ICP0","volume":"78","author":"Y Sato","year":"2016","journal-title":"J Vet Med Sci"},{"key":"ppat.1010588.ref085","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.virol.2015.02.033","article-title":"Ubiquitination in the antiviral immune response","volume":"479\u2013480","author":"ME Davis","year":"2015","journal-title":"Virology"},{"issue":"4","key":"ppat.1010588.ref086","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/10409238.2017.1325829","article-title":"Ubiquitin enzymes in the regulation of immune responses","volume":"52","author":"P Ebner","year":"2017","journal-title":"Crit Rev Biochem Mol Biol"},{"issue":"13","key":"ppat.1010588.ref087","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.4161\/cbt.21792","article-title":"Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil","volume":"13","author":"DR Harris","year":"2012","journal-title":"Cancer Biol Ther"},{"issue":"3","key":"ppat.1010588.ref088","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method for estimating fifty per cent endpoints","volume":"27","author":"LJ Reed","year":"1938","journal-title":"American journal of epidemiology"},{"issue":"8","key":"ppat.1010588.ref089","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.prot095562","article-title":"Measuring the Infectious Titer of Recombinant Adenovirus Using Tissue Culture Infection Dose 50% (TCID50) End-Point Dilution and Quantitative Polymerase Chain Reaction (qPCR).","volume":"2019","author":"M Lock","year":"2019","journal-title":"Cold Spring Harb Protoc"},{"key":"ppat.1010588.ref090","doi-asserted-by":"crossref","first-page":"729837","DOI":"10.3389\/fimmu.2021.729837","article-title":"Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge.","volume":"12","author":"E Gabitzsch","year":"2021","journal-title":"Front Immunol."},{"issue":"4","key":"ppat.1010588.ref091","doi-asserted-by":"crossref","first-page":"e1000841","DOI":"10.1371\/journal.ppat.1000841","article-title":"Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis.","volume":"6","author":"AV Chintakuntlawar","year":"2010","journal-title":"PLoS Pathog."},{"issue":"11","key":"ppat.1010588.ref092","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/1044-0305(94)80016-2","article-title":"An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database","volume":"5","author":"JK Eng","year":"1994","journal-title":"J Am Soc Mass Spectrom"},{"issue":"8","key":"ppat.1010588.ref093","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nmeth.2557","article-title":"The CRAPome: a contaminant repository for affinity purification-mass spectrometry data","volume":"10","author":"D Mellacheruvu","year":"2013","journal-title":"Nat Methods"},{"key":"ppat.1010588.ref094","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.3389\/fmicb.2018.02178","article-title":"Adenoviromics: Mining the Human Adenovirus Species D Genome.","volume":"9","author":"AM Ismail","year":"2018","journal-title":"Front Microbiol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010588","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000}}],"container-title":["PLOS 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