{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:04:58Z","timestamp":1791331498849,"version":"4.3.1"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Of the 24 known measles genotypes, only D8 and B3 are responsible for outbreaks in the last years in Europe, Asia, and America. In this study the H gene of 92 strains circulating between 2015 and 2019 in Lombardy, Northern Italy, and 1273 H sequences available in GenBank were analyzed in order to evaluate the genetic variability and to assess the conservation of the immunodominant sites. Overall, in Lombardy we observed the presence of four different B3 and three different D8 clusters, each one of them including sequences derived from viruses found in both vaccinated and unvaccinated subjects. Worldwide, the residue 400 within the H protein, a position located within the main immune epitope, is mutated in all circulating strains that belong to the two globally endemic genotypes, B3 and D8. Our data demonstrate the usefulness of measles virus (MV) H gene sequencing. Indeed, the monitoring the H protein epitopes of circulating strains could be included in the measles laboratory surveillance activities in order to improve and optimize strategies for measles control, as countries go towards elimination phase.<\/jats:p>","DOI":"10.3390\/ijms21124435","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T06:11:02Z","timestamp":1592892662000},"page":"4435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Molecular Epidemiology of B3 and D8 Measles Viruses through Hemagglutinin Phylogenetic History"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-9408","authenticated-orcid":false,"given":"Silvia","family":"Bianchi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-128X","authenticated-orcid":false,"given":"Marta","family":"Canuti","sequence":"additional","affiliation":[{"name":"Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Ave., St. John\u2019s, NL A1B 3X9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-5856","authenticated-orcid":false,"given":"Giulia","family":"Ciceri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-2791","authenticated-orcid":false,"given":"Maria","family":"Gori","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Colzani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Dura","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Marina","family":"Pennati","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Baggieri","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, National Reference Laboratory for Measles and Rubella, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Magurano","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, National Reference Laboratory for Measles and Rubella, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-701X","authenticated-orcid":false,"given":"Elisabetta","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"},{"name":"Coordinated Research Center \u201cEpiSoMI\u201d, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Amendola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"},{"name":"Coordinated Research Center \u201cEpiSoMI\u201d, University of Milan, via Carlo Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1099\/jgv.0.001328","article-title":"ICTV Virus Taxonomy Profile: Paramyxoviridae","volume":"100","author":"Rima","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1016\/S0140-6736(17)31463-0","article-title":"Measles","volume":"390","author":"Moss","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.15585\/mmwr.mm6747a6","article-title":"Progress Toward Regional Measles Elimination-Worldwide, 2000-2017","volume":"67","author":"Dabbagh","year":"2018","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"893","DOI":"10.15585\/mmwr.mm6840e2","article-title":"National Update on Measles Cases and Outbreaks-United States, January 1-October 1, 2019","volume":"68","author":"Patel","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Patel, M.K., and Orenstein, W.A. (2019). Classification of global measles cases in 2013\u201317 as due to policy or vaccination failure: A retrospective review of global surveillance data. Lancet, 7.","DOI":"10.1016\/S2214-109X(18)30492-3"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hashiguchi, T., Maenaka, K., and Yanagi, Y. (2011). Measles Virus Hemagglutinin: Structural Insights into Cell Entry and Measles Vaccine. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00247"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1080\/21645515.2015.1122146","article-title":"Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination","volume":"12","author":"Baldo","year":"2016","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tahara, M., B\u00fcrckert, J.-P., Kanou, K., Maenaka, K., Muller, C.P., and Takeda, M. (2016). Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability. Viruses, 8.","DOI":"10.3390\/v8080216"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/cid\/ciu105","article-title":"Outbreak of measles among persons with prior evidence of immunity, New York City, 2011","volume":"58","author":"Rosen","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S559","DOI":"10.1093\/infdis\/jir098","article-title":"Two case studies of modified measles in vaccinated physicians exposed to primary measles cases: High risk of infection but low risk of transmission","volume":"204","author":"Rota","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1093\/cid\/ciy286","article-title":"Clinical Characteristics of Measles in Previously Vaccinated and Unvaccinated Patients in California","volume":"67","author":"Cherry","year":"2018","journal-title":"Clin. Inf. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/00006454-199601000-00014","article-title":"Secondary failure rates of measles vaccines: A metaanalysis of published studies","volume":"15","author":"Anders","year":"1996","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s10654-019-00569-4","article-title":"Measles, the need for a paradigm shift","volume":"34","author":"Javelle","year":"2019","journal-title":"Eur. J. Epidemiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S514","DOI":"10.1093\/infdis\/jir118","article-title":"Global distribution of measles genotypes and measles molecular epidemiology","volume":"204","author":"Rota","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.15585\/mmwr.mm6517a3","article-title":"Global Measles and Rubella Laboratory Network Support for Elimination Goals, 2010-2015","volume":"65","author":"Mulders","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.virusres.2017.05.009","article-title":"Towards measles elimination in Italy: Virological surveillance and genotypes trend (2013-2015)","volume":"236","author":"Magurano","year":"2017","journal-title":"Virus Res."},{"key":"ref_17","unstructured":"Expanded Programme on Immunization (EPI) (1998). Standardization of the nomenclature for describing the genetic characteristics of wild-type measles viruses. Wkly. Epidemiol. Rec., 73, 265\u2013269."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1099\/vir.0.013524-0","article-title":"Measles viruses of genotype H1 evade recognition by vaccine-induced neutralizing antibodies targeting the linear haemagglutinin noose epitope","volume":"90","author":"Finsterbusch","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11547","DOI":"10.1128\/JVI.79.17.11547-11551.2005","article-title":"Relative contributions of measles virus hemagglutinin- and fusion protein-specific serum antibodies to virus neutralization","volume":"79","author":"Osterhaus","year":"2005","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1089\/088282402760312331","article-title":"Neutralizing B cell response in measles","volume":"15","author":"Bouche","year":"2002","journal-title":"Viral Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1099\/vir.0.014944-0","article-title":"Depletion of measles virus glycoprotein-specific antibodies from human sera reveals genotype-specific neutralizing antibodies","volume":"90","author":"Langerijs","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1128\/JVI.03029-12","article-title":"The receptor-binding site of the measles virus hemagglutinin protein itself constitutes a conserved neutralizing epitope","volume":"87","author":"Tahara","year":"2013","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11262-011-0638-0","article-title":"Measles incidence rate and a phylogenetic study of contemporary genotype H1 measles strains in China: Is an improved measles vaccine needed?","volume":"43","author":"Shi","year":"2011","journal-title":"Virus Genes"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ciceri, G., Canuti, M., Bianchi, S., Gori, M., Piralla, A., Colzani, D., Libretti, M., Frati, E.R., Baggieri, M., and Lai, A. (2019). Genetic variability of the measles virus hemagglutinin gene in B3 genotype strains circulating in Northern Italy. Infect. Genet. Evol., 75.","DOI":"10.1016\/j.meegid.2019.103943"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"FUBAR: A fast, unconstrained bayesian approximation for inferring selection","volume":"30","author":"Murrell","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Murrell, B., Wertheim, J.O., Moola, S., Weighill, T., Scheffler, K., and Kosakovsky Pond, S.L. (2012). Detecting individual sites subject to episodic diversifying selection. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002764"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01734359","article-title":"Evolutionary trees from DNA sequences: A maximum likelihood approach","volume":"17","author":"Felsenstein","year":"1981","journal-title":"J. Mol. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF01731581","article-title":"A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences","volume":"16","author":"Kimura","year":"1980","journal-title":"J. Mol. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2307\/2408678","article-title":"Confidence limits on phylogenies: An approach using the bootstrap","volume":"39","author":"Felsenstein","year":"1985","journal-title":"Evolution"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0168-1702(98)00018-5","article-title":"Genetic and antigenic characterisation of the haemagglutinin protein of measles virus strains recently circulating in the UK","volume":"55","author":"Jin","year":"1998","journal-title":"Virus Res."},{"key":"ref_32","first-page":"678","article-title":"Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G+C-content biases","volume":"9","author":"Tamura","year":"1992","journal-title":"Mol. Biol. Evol."},{"key":"ref_33","unstructured":"(2020, April 29). 8th Meeting of the European Regional Verification Commission for Measles and Rubella Elimination (RVC) (2019). Available online: http:\/\/www.euro.who.int\/en\/health-topics\/communicable-diseases\/measles-and-rubella\/publications\/2019\/8th-meeting-of-the-european-regional-verification-commission-for-measles-and-rubella-elimination-rvc-2019."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/1743-422X-9-284","article-title":"Molecular epidemiology of measles virus in Italy, 2002\u20132007","volume":"9","author":"Magurano","year":"2012","journal-title":"Virol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.meegid.2016.12.013","article-title":"Measles re-emergence in Northern Italy: Pathways of measles virus genotype D8, 2013-2014","volume":"48","author":"Amendola","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jcv.2014.12.019","article-title":"Measles elimination in Italy: Data from laboratory activity, 2011-2013","volume":"64","author":"Magurano","year":"2015","journal-title":"J. Clin. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Filia, A., Amendola, A., Faccini, M., Del Manso, M., Senatore, S., Bianchi, S., Borrini, B.M., Ciampelli, A., Tanzi, E., and Filipponi, M.T. (2016). Outbreak of a new measles B3 variant in the Roma\/Sinti population with transmission in the nosocomial setting, Italy, November 2015 to April 2016. Euro Surveill., 21.","DOI":"10.2807\/1560-7917.ES.2016.21.20.30235"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Amendola, A., Bianchi, S., Frati, E.R., Ciceri, G., Faccini, M., Senatore, S., Colzani, D., Lamberti, A., Baggieri, M., and Cereda, D. (2017). Ongoing large measles outbreak with nosocomial transmission in Milan, northern Italy, March-August 2017. Euro Surveill., 22.","DOI":"10.2807\/1560-7917.ES.2017.22.33.30596"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bianchi, S., Frati, E.R., Lai, A., Colzani, D., Ciceri, G., Baggieri, M., Lamberti, A., Senatore, S., Faccini, M., and Mazzilli, F. (2019). Genetic characterisation of Measles virus variants identified during a large epidemic in Milan, Italy, March-December 2017. Epidemiol. Infect., 147.","DOI":"10.1017\/S0950268818003606"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/cid\/ciy306","article-title":"Measles in Vaccinated Individuals and the Future of Measles Elimination","volume":"67","author":"Moss","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","unstructured":"Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., and Darnell, J. (2000). Hierarchical Structure of Proteins. Molecular Cell Biology, W. H. FReeman. [4th ed.]."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_43","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_44","unstructured":"(2020, April 11). Centers for Disease Control and Prevention Genetic Analysis of Measles Virus, Available online: https:\/\/www.cdc.gov\/measles\/lab-tools\/genetic-analysis.html."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3201\/eid1606.100089","article-title":"New Measles Virus Genotype Associated with Outbreak, China","volume":"16","author":"Wang","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/bioinformatics\/16.6.562","article-title":"RDP: Detection of recombination amongst aligned sequences","volume":"16","author":"Martin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","article-title":"HyPhy: Hypothesis testing using phylogenies","volume":"21","author":"Pond","year":"2005","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:41:12Z","timestamp":1760175672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21124435"],"URL":"https:\/\/doi.org\/10.3390\/ijms21124435","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]}}}