{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T03:53:21Z","timestamp":1771991601166,"version":"3.50.1"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T00:00:00Z","timestamp":1258416000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0007870","type":"journal-article","created":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T00:05:33Z","timestamp":1258416333000},"page":"e7870","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":147,"title":["Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro"],"prefix":"10.1371","volume":"4","author":[{"given":"Yiu-Wing","family":"Kam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuushi","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa F. P.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Bruzzone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Altmeyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2009,11,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0966-842X(93)90112-5","article-title":"Protease-dependent virus tropism and pathogenicity.","volume":"1","author":"Y Nagai","year":"1993","journal-title":"Trends Microbiol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0966-842X(94)90123-6","article-title":"Host cell proteases controlling virus pathogenicity.","volume":"2","author":"HD Klenk","year":"1994","journal-title":"Trends Microbiol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0092-8674(88)90487-4","article-title":"Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus.","volume":"53","author":"JM McCune","year":"1988","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0042-6822(75)90285-8","article-title":"Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide.","volume":"68","author":"SG Lazarowitz","year":"1975","journal-title":"Virology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1016-8478(23)13535-7","article-title":"Cellular proteinases trigger the infectivity of the influenza A and Sendai viruses.","volume":"9","author":"H Kido","year":"1999","journal-title":"Mol Cells"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0065-3527(08)60520-5","article-title":"The molecular biology of influenza virus pathogenicity.","volume":"34","author":"HD Klenk","year":"1988","journal-title":"Adv Virus Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF01309262","article-title":"Evidence of proteolytic activation of Sendai virus in mouse lung.","volume":"77","author":"M Tashiro","year":"1983","journal-title":"Arch Virol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1099\/0022-1317-50-1-135","article-title":"Mutational changes of the protease susceptibility of glycoprotein F of Newcastle disease virus: effects on pathogenicity.","volume":"50","author":"W Garten","year":"1980","journal-title":"J Gen Virol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"13573","DOI":"10.1016\/S0021-9258(18)42250-8","article-title":"Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein.","volume":"267","author":"H Kido","year":"1992","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1046\/j.1432-1327.2001.02166.x","article-title":"Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus.","volume":"268","author":"M Murakami","year":"2001","journal-title":"Eur J Biochem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1046\/j.1432-1033.2002.02937.x","article-title":"Identification of ectopic anionic trypsin I in rat lungs potentiating pneumotropic virus infectivity and increased enzyme level after virus infection.","volume":"269","author":"T Towatari","year":"2002","journal-title":"Eur J Biochem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1046\/j.1432-1327.2000.01346.x","article-title":"Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses. Purification and characterization.","volume":"267","author":"Y Chen","year":"2000","journal-title":"Eur J Biochem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1515\/BC.2003.024","article-title":"A novel influenza A virus activating enzyme from porcine lung: purification and characterization.","volume":"384","author":"M Sato","year":"2003","journal-title":"Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/IAI.31.3.1214-1222.1981","article-title":"Enhancement of plaque formation and cell fusion of an enteropathogenic coronavirus by trypsin treatment.","volume":"31","author":"J Storz","year":"1981","journal-title":"Infect Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF01311303","article-title":"Susceptibility of rodent cell lines to rat coronaviruses and differential enhancement by trypsin or DEAE-dextran.","volume":"118","author":"DJ Gaertner","year":"1991","journal-title":"Arch Virol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-4615-5331-1_12","article-title":"Requirement of proteolytic cleavage of the murine coronavirus MHV-2 spike protein for fusion activity.","volume":"440","author":"YK Yamada","year":"1998","journal-title":"Adv Exp Med Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"366","DOI":"10.2307\/1592976","article-title":"Spike glycoprotein cleavage recognition site analysis of infectious bronchitis virus.","volume":"45","author":"MW Jackwood","year":"2001","journal-title":"Avian Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1128\/JVI.56.3.912-920.1985","article-title":"Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion.","volume":"56","author":"MF Frana","year":"1985","journal-title":"J Virol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF01309637","article-title":"Comparison of hemagglutinating, receptor-destroying, and acetylesterase activities of avirulent and virulent bovine coronavirus strains.","volume":"125","author":"J Storz","year":"1992","journal-title":"Arch Virol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1128\/JVI.67.8.4504-4512.1993","article-title":"Fusion-defective mutants of mouse hepatitis virus A59 contain a mutation in the spike protein cleavage signal.","volume":"67","author":"JL Gombold","year":"1993","journal-title":"J Virol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1128\/JVI.56.3.904-911.1985","article-title":"Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90 K cleavage fragments.","volume":"56","author":"LS Sturman","year":"1985","journal-title":"J Virol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.1085952","article-title":"Characterization of a novel coronavirus associated with severe acute respiratory syndrome.","volume":"300","author":"PA Rota","year":"2003","journal-title":"Science"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1073\/pnas.0306446101","article-title":"Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry.","volume":"101","author":"G Simmons","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"12543","DOI":"10.1073\/pnas.0503203102","article-title":"Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection.","volume":"102","author":"S Matsuyama","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/0042-6822(75)90284-6","article-title":"Activation of influenza A viruses by trypsin treatment.","volume":"68","author":"HD Klenk","year":"1975","journal-title":"Virology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e1082","DOI":"10.1371\/journal.pone.0001082","article-title":"Conformational reorganization of the SARS coronavirus spike following receptor binding: implications for membrane fusion.","volume":"2","author":"DR Beniac","year":"2007","journal-title":"PLoS ONE"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1073\/pnas.0809524106","article-title":"Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.","volume":"106","author":"S Belouzard","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJMoa032867","article-title":"Evidence of airborne transmission of the severe acute respiratory syndrome virus.","volume":"350","author":"IT Yu","year":"2004","journal-title":"N Engl J Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(03)13413-7","article-title":"Lung pathology of fatal severe acute respiratory syndrome.","volume":"361","author":"JM Nicholls","year":"2003","journal-title":"Lancet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.bbrc.2004.07.060","article-title":"Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression.","volume":"321","author":"Y Nie","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"14614","DOI":"10.1128\/JVI.79.23.14614-14621.2005","article-title":"ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia.","volume":"79","author":"HP Jia","year":"2005","journal-title":"J Virol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1126\/science.1116480","article-title":"Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.","volume":"309","author":"F Li","year":"2005","journal-title":"Science"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.vaccine.2006.08.011","article-title":"Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro.","volume":"25","author":"YW Kam","year":"2007","journal-title":"Vaccine"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"12463","DOI":"10.1128\/JVI.76.24.12463-12472.2002","article-title":"Covalent modifications of the ebola virus glycoprotein.","volume":"76","author":"SA Jeffers","year":"2002","journal-title":"J Virol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrm1052","article-title":"Quality control in the endoplasmic reticulum.","volume":"4","author":"L Ellgaard","year":"2003","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1128\/JVI.02205-08","article-title":"Proteolytic activation of the 1918 influenza virus hemagglutinin.","volume":"83","author":"C Chaipan","year":"2009","journal-title":"J Virol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0042-6822(03)00264-2","article-title":"Human influenza A viruses are proteolytically activated and do not induce apoptosis in CACO-2 cells.","volume":"313","author":"O Zhirnov","year":"2003","journal-title":"Virology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1128\/JVI.79.6.3846-3850.2005","article-title":"Exogenous ACE2 expression allows refractory cell lines to support severe acute respiratory syndrome coronavirus replication.","volume":"79","author":"EC Mossel","year":"2005","journal-title":"J Virol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1128\/JVI.78.11.5642-5650.2004","article-title":"pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN.","volume":"78","author":"ZY Yang","year":"2004","journal-title":"J Virol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.","volume":"426","author":"W Li","year":"2003","journal-title":"Nature"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bbrc.2004.01.076","article-title":"Expression cloning of functional receptor used by SARS coronavirus.","volume":"315","author":"P Wang","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/path.1560","article-title":"Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways.","volume":"203","author":"Y Ding","year":"2004","journal-title":"J Pathol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0014-5793(02)03640-2","article-title":"Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme.","volume":"532","author":"D Harmer","year":"2002","journal-title":"FEBS Lett"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1165\/ajrcmb.10.1.7507342","article-title":"CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells.","volume":"10","author":"AL Cozens","year":"1994","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref45","first-page":"1904","article-title":"Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes.","volume":"48","author":"RR Reddel","year":"1988","journal-title":"Cancer Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/(SICI)1097-0029(19970901)38:5<488::AID-JEMT5>3.0.CO;2-E","article-title":"Human airway epithelial tight junctions.","volume":"38","author":"RW Godfrey","year":"1997","journal-title":"Microsc Res Tech"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1183\/09031936.99.13613299","article-title":"Cytokine-induced airway epithelial ICAM-1 upregulation: quantification by high-resolution scanning and transmission electron microscopy.","volume":"13","author":"J Zhu","year":"1999","journal-title":"Eur Respir J"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0092-8674(01)00418-4","article-title":"Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses.","volume":"106","author":"SY Chan","year":"2001","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/381661a0","article-title":"Identification of a major co-receptor for primary isolates of HIV-1.","volume":"381","author":"H Deng","year":"1996","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1128\/JVI.72.4.3155-3160.1998","article-title":"Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines.","volume":"72","author":"RJ Wool-Lewis","year":"1998","journal-title":"J Virol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"8887","DOI":"10.1128\/JVI.00415-08","article-title":"Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide.","volume":"82","author":"BJ Bosch","year":"2008","journal-title":"J Virol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"11985","DOI":"10.1128\/JVI.01412-08","article-title":"Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved S protein as revealed by pseudotype virus bearing cleaved S protein.","volume":"82","author":"R Watanabe","year":"2008","journal-title":"J Virol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-4615-1325-4_29","article-title":"Receptor specificity and receptor-induced conformational changes in mouse hepatitis virus spike glycoprotein.","volume":"494","author":"KV Holmes","year":"2001","journal-title":"Adv Exp Med Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1128\/JVI.77.2.830-840.2003","article-title":"Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37 degrees C either by soluble murine CEACAM1 receptors or by pH 8.","volume":"77","author":"BD Zelus","year":"2003","journal-title":"J Virol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1146\/annurev.biochem.70.1.777","article-title":"Mechanisms of viral membrane fusion and its inhibition.","volume":"70","author":"DM Eckert","year":"2001","journal-title":"Annu Rev Biochem"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/096876899294706","article-title":"Structural basis for membrane fusion by enveloped viruses.","volume":"16","author":"W Weissenhorn","year":"1999","journal-title":"Mol Membr Biol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1515\/BC.2004.133","article-title":"Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential.","volume":"385","author":"H Kido","year":"2004","journal-title":"Biol Chem"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1099\/vir.0.80671-0","article-title":"Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E.","volume":"86","author":"B Nal","year":"2005","journal-title":"J Gen Virol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4.","volume":"227","author":"UK Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"32035","DOI":"10.1074\/jbc.M402296200","article-title":"C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles.","volume":"279","author":"PY Lozach","year":"2004","journal-title":"J Biol Chem"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1128\/JVI.77.7.4070-4080.2003","article-title":"Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR.","volume":"77","author":"S Pohlmann","year":"2003","journal-title":"J Virol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1006\/viro.1995.1016","article-title":"Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes.","volume":"206","author":"RI Connor","year":"1995","journal-title":"Virology"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0007870","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T17:47:31Z","timestamp":1710697651000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0007870"}},"subtitle":[],"editor":[{"given":"Georges","family":"Snounou","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2009,11,17]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2009,11,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0007870","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,17]]}}}