{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:35:33Z","timestamp":1790674533189,"version":"4.1.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T00:00:00Z","timestamp":1433980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0128982","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T17:56:07Z","timestamp":1434045367000},"page":"e0128982","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identification of Influenza A\/PR\/8\/34 Donor Viruses Imparting High Hemagglutinin Yields to Candidate Vaccine Viruses in Eggs"],"prefix":"10.1371","volume":"10","author":[{"given":"Adam","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Winne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen G.","family":"Metcalfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guaniri","family":"Mateu-Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie","family":"Ridenour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Jaber","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Villanueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif R.","family":"Zaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracie L.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben O.","family":"Donis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,6,11]]},"reference":[{"key":"ref1","article-title":"The Bridge","author":"JT Matthews","year":"2006"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e30018","DOI":"10.1371\/journal.pone.0030018","article-title":"Effect of vaccines and antivirals during the major 2009 A(H1N1) pandemic wave in Norway\u2014and the influence of vaccination timing","volume":"7","author":"BF Blasio","year":"2012","journal-title":"PLoS One"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"e1001076","DOI":"10.1371\/journal.pcbi.1001076","article-title":"Mitigation strategies for pandemic influenza A: balancing conflicting policy objectives","volume":"7","author":"TD Hollingsworth","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"5935","DOI":"10.1073\/pnas.0601266103","article-title":"Mitigation strategies for pandemic influenza in the United States","volume":"103","author":"TC Germann","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref5","unstructured":"WHO (2006) A review of production technologies for influenza virus vaccines, and their suitability for deployment in developing countries for influenza pandemic preparedness. In: Research IfV, editor. Geneva."},{"key":"ref6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/infdis\/124.5.449","article-title":"Related studies of a recombinant influenza-virus vaccine. I. Derivation and characterization of virus and vaccine","volume":"124","author":"ED Kilbourne","year":"1971","journal-title":"J Infect Dis"},{"key":"ref7","first-page":"643","article-title":"Future influenza vaccines and the use of genetic recombinants","volume":"41","author":"ED Kilbourne","year":"1969","journal-title":"Bull World Health Organ"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/infdis\/141.3.362","article-title":"Gene composition of high-yielding influenza vaccine strains obtained by recombination","volume":"141","author":"M Baez","year":"1980","journal-title":"J Infect Dis"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.virol.2007.07.002","article-title":"Enhanced growth of seed viruses for H5N1 influenza vaccines","volume":"366","author":"T Horimoto","year":"2007","journal-title":"Virology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.coviro.2011.08.002","article-title":"Influenza virus vaccines: lessons from the 2009 H1N1 pandemic","volume":"1","author":"AJ Broadbent","year":"2011","journal-title":"Curr Opin Virol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1128\/JVI.00096-11","article-title":"Improved antigen yield in pandemic H1N1 (2009) candidate vaccine viruses with chimeric hemagglutinin molecules","volume":"85","author":"R Harvey","year":"2011","journal-title":"J Virol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.molmed.2006.09.003","article-title":"Strategies for developing vaccines against H5N1 influenza A viruses","volume":"12","author":"T Horimoto","year":"2006","journal-title":"Trends Mol Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1016\/j.vaccine.2012.04.073","article-title":"Increased hemagglutinin content in a reassortant 2009 pandemic H1N1 influenza virus with chimeric neuraminidase containing donor A\/Puerto Rico\/8\/34 virus transmembrane and stalk domains","volume":"30","author":"X Jing","year":"2012","journal-title":"Vaccine"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e65955","DOI":"10.1371\/journal.pone.0065955","article-title":"Molecular signature of high yield (growth) influenza a virus reassortants prepared as candidate vaccine seeds","volume":"8","author":"M Ramanunninair","year":"2013","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1016\/j.vaccine.2010.12.044","article-title":"The development of vaccine viruses against pandemic A(H1N1) influenza","volume":"29","author":"JS Robertson","year":"2011","journal-title":"Vaccine"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.vaccine.2011.11.081","article-title":"An additional oligosaccharide moiety in the HA of a pandemic influenza H1N1 candidate vaccine virus confers increased antigen yield in eggs","volume":"30","author":"C Nicolson","year":"2012","journal-title":"Vaccine"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1128\/JVI.79.11.6763-6771.2005","article-title":"Improvement of influenza A\/Fujian\/411\/02 (H3N2) virus growth in embryonated chicken eggs by balancing the hemagglutinin and neuraminidase activities, using reverse genetics","volume":"79","author":"B Lu","year":"2005","journal-title":"J Virol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1016\/j.vaccine.2005.07.005","article-title":"The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate","volume":"24","author":"T Horimoto","year":"2006","journal-title":"Vaccine"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1128\/JVI.00970-08","article-title":"Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells","volume":"82","author":"S Murakami","year":"2008","journal-title":"J Virol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(04)15892-3","article-title":"Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines","volume":"363","author":"RJ Webby","year":"2004","journal-title":"Lancet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1006\/viro.2002.1742","article-title":"Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics","volume":"305","author":"K Subbarao","year":"2003","journal-title":"Virology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.3201\/eid1110.050644","article-title":"Evolution of H5N1 Avian Influenza Viruses in Asia","volume":"11","year":"2005","journal-title":"Emerg Infect Dis"},{"key":"ref23","unstructured":"FLUSECURE (2005) 2005207 FLUSECURE Project Technical Report 2 Towards sufficiency of Pandemic Influenza vaccines in the EU."},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1099\/0022-1317-81-5-1283","article-title":"Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses","volume":"81","author":"N Naffakh","year":"2000","journal-title":"J Gen Virol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1002443","DOI":"10.1371\/journal.ppat.1002443","article-title":"Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus","volume":"7","author":"SS Lakdawala","year":"2011","journal-title":"PLoS Pathog"},{"key":"ref26","first-page":"269","article-title":"Native morphology of influenza virions","volume":"2","author":"T Noda","year":"2011","journal-title":"Front Microbiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/viro.1997.8916","article-title":"The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation","volume":"240","author":"PC Roberts","year":"1998","journal-title":"Virology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1016\/j.vaccine.2011.05.036","article-title":"Improvement of H5N1 influenza vaccine viruses: influence of internal gene segments of avian and human origin on production and hemagglutinin content","volume":"29","author":"M Abt","year":"2011","journal-title":"Vaccine"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1128\/JVI.02856-12","article-title":"The Source of the PB1 Gene in Influenza Vaccine Reassortants Selectively Alters the Hemagglutinin Content of the Resulting Seed Virus","volume":"87","author":"JC Cobbin","year":"2013","journal-title":"J Virol"},{"key":"ref30","unstructured":"WHO (2013) Update of WHO biosafety risk assessment and guidelines for the production and quality control of human influenza vaccines against avian influenza A(H7N9) virus. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/entity\/biologicals\/areas\/vaccines\/influenza\/biosafety_risk_assessment_10may2013.pdf\" xlink:type=\"simple\">http:\/\/www.who.int\/entity\/biologicals\/areas\/vaccines\/influenza\/biosafety_risk_assessment_10may2013.pdf<\/ext-link>."},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.vaccine.2010.11.042","article-title":"Lessons from pandemic influenza A(H1N1): the research-based vaccine industry&apos;s perspective","volume":"29","author":"A Abelin","year":"2011","journal-title":"Vaccine"},{"key":"ref32","first-page":"405","article-title":"Production of pilot lots of inactivated influenza vaccine in response to a pandemic threat: an interim biosafety risk assessment","volume":"78","year":"2003","journal-title":"Wkly Epidemiol Rec"},{"key":"ref33","article-title":"Report to the President on Reengineering the Influenza Vaccine Production Enterprise to Meet the Challenges of Pandemic Influenza","year":"2010"},{"key":"ref34","unstructured":"PHEMCE (2012) 2012 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy."},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1128\/JVI.02391-08","article-title":"Optimizing viral protein yield of influenza virus strain a\/vietnam\/1203\/2004 by modification of the neuraminidase gene","volume":"83","author":"JE Adamo","year":"2009","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/oxfordjournals.molbev.a026057","article-title":"Positive selection on the H3 hemagglutinin gene of human influenza virus A","volume":"16","author":"RM Bush","year":"1999","journal-title":"Mol Biol Evol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1006\/viro.1999.9732","article-title":"Effects of egg-adaptation on the receptor-binding properties of human influenza A and B viruses","volume":"258","author":"AS Gambaryan","year":"1999","journal-title":"Virology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.1128\/JVI.00058-10","article-title":"Receptor specificity of influenza A H3N2 viruses isolated in mammalian cells and embryonated chicken eggs","volume":"84","author":"J Stevens","year":"2010","journal-title":"J Virol"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Widjaja L, Ilyushina N, Webster RG, Webby RJ (2006) Molecular changes associated with adaptation of human influenza A virus in embryonated chicken eggs. Virology.","DOI":"10.1016\/j.virol.2006.02.020"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e46378","DOI":"10.1371\/journal.pone.0046378","article-title":"Partial and full PCR-based reverse genetics strategy for influenza viruses","volume":"7","author":"H Chen","year":"2012","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1007\/s00705-006-0931-8","article-title":"Effect of gene constellation and postreassortment amino acid change on the phenotypic features of H5 influenza virus reassortants","volume":"152","author":"IA Rudneva","year":"2007","journal-title":"Arch Virol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.virol.2011.03.011","article-title":"Importance of viral genomic composition in modulating glycoprotein content on the surface of influenza virus particles","volume":"414","author":"V Moules","year":"2011","journal-title":"Virology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1128\/JVI.03354-13","article-title":"Specific nucleoprotein residues affect influenza virus morphology","volume":"88","author":"KM Bialas","year":"2014","journal-title":"J Virol"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Harvey R, Wheeler JX, Wallis CL, Robertson JS, Engelhardt OG (2008) Quantitation of haemagglutinin in H5N1 influenza viruses reveals low haemagglutinin content of vaccine virus NIBRG-14 (H5N1). Vaccine.","DOI":"10.1016\/j.vaccine.2008.09.050"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1083\/jcb.133.3.559","article-title":"Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers","volume":"133","author":"T Danieli","year":"1996","journal-title":"J Cell Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.1073\/pnas.1200987109","article-title":"Influenza A virus entry into cells lacking sialylated N-glycans","volume":"109","author":"E de Vries","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"e88288","DOI":"10.1371\/journal.pone.0088288","article-title":"Morphology of influenza B\/Lee\/40 determined by cryo-electron microscopy","volume":"9","author":"G Katz","year":"2014","journal-title":"PLoS One"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.chom.2014.01.006","article-title":"A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability","volume":"15","author":"R Beale","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Sugita Y, Noda T, Sagara H, Kawaoka Y (2011) Ultracentrifugation Deforms Unfixed Influenza A Virions. J Gen Virol.","DOI":"10.1099\/vir.0.036715-0"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"13343","DOI":"10.1128\/JVI.02004-13","article-title":"Spherical Influenza Viruses Have a Fitness Advantage in Embryonated Eggs, while Filament-Producing Strains Are Selected In Vivo","volume":"87","author":"J Seladi-Schulman","year":"2013","journal-title":"J Virol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"9973","DOI":"10.1128\/JVI.01363-13","article-title":"The amphipathic helix of influenza A virus M2 protein is required for filamentous bud formation and scission of filamentous and spherical particles","volume":"87","author":"KL Roberts","year":"2013","journal-title":"J Virol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1128\/JVI.00119-10","article-title":"Influenza virus m2 ion channel protein is necessary for filamentous virion formation","volume":"84","author":"JS Rossman","year":"2010","journal-title":"J Virol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.vaccine.2012.10.060","article-title":"Mutations to A\/Puerto Rico\/8\/34 PB1 gene improves seasonal reassortant influenza A virus growth kinetics","volume":"31","author":"EP Plant","year":"2012","journal-title":"Vaccine"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.1016\/j.vaccine.2010.09.006","article-title":"Improved haemagglutinin antigen content in H5N1 candidate vaccine viruses with chimeric haemagglutinin molecules","volume":"28","author":"R Harvey","year":"2010","journal-title":"Vaccine"},{"key":"ref55","unstructured":"FDA (2012) Summary Basis of Regulatory Action; FLUCELVAX. In: HHS, editor. Washington, DC."},{"key":"ref56","unstructured":"WHO-GISRS (2015) Influenza vaccine viruses and reagents. In: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/influenza\/vaccines\/virus\/en\/\" xlink:type=\"simple\">http:\/\/www.who.int\/influenza\/vaccines\/virus\/en\/<\/ext-link>, editor."},{"key":"ref57","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1365-2818.1973.tb04625.x","article-title":"Wetting agents for biological electron microscopy. I. General considerations and negative staining","volume":"99","author":"DW Gregory","year":"1973","journal-title":"J Microsc"},{"key":"ref58","first-page":"17","article-title":"Recent Developments in Negative Staining for Transmission Electron Microscopy","volume":"20","author":"J.R. H","year":"2006","journal-title":"Microsc Anal"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/j.vaccine.2011.12.056","article-title":"Simultaneous quantification of hemagglutinin and neuraminidase of influenza virus using isotope dilution mass spectrometry","volume":"30","author":"TL Williams","year":"2012","journal-title":"Vaccine"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1016\/j.vaccine.2008.03.014","article-title":"Quantification of influenza virus hemagglutinins in complex mixtures using isotope dilution tandem mass spectrometry","volume":"26","author":"TL Williams","year":"2008","journal-title":"Vaccine"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Santana WI, Williams TL, Winne EK, Pirkle JL, Barr JR (2014) Quantification of Viral Proteins of the Avian H7 Subtype of In fl uenza Virus-An Isotope Dilution Mass Spectrometry Method Applicable for Producing more Rapid Vaccines in the Case of an Influenza Pandemic. Anal Chem.","DOI":"10.1021\/ac4040778"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0128982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T03:07:08Z","timestamp":1588993628000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0128982"}},"subtitle":[],"editor":[{"given":"Ralph","family":"Tripp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,6,11]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0128982","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,11]]}}}