{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:40:16Z","timestamp":1778035216880,"version":"3.51.4"},"reference-count":64,"publisher":"Microbiology Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:p>Wild-type mumps viruses (MuVs) are highly neurotropic and, prior to widespread vaccination programmes, were a major cause of viral meningitis and encephalitis in most developed countries. At present, there are no markers for virus attenuation, apart from the failure of a passaged isolate to produce clinical symptoms in vaccinees. Indeed, some MuV vaccines have retained residual neurovirulence properties and have caused aseptic meningitis in vaccinees. Three amino acid changes associated with the neuroattenuation of a wild-type MuV strain were identified previously. This study evaluated the impact of these changes on the function of the respective proteins. The data demonstrated that the Ser\u2192Asp amino acid substitution at position 466 in the haemagglutinin\u2013neuraminidase protein resulted in decreased receptor binding and neuraminidase activity, the Ala\/Thr\u2192Thr selection in the fusion protein resulted in decreased fusion activity, and the Ile\u2192Val substitution in the polymerase resulted in increased replicative\/transcriptional activity. These data suggest a polygenic component (i.e. specific and inter-related roles of these amino acid changes) to MuV neuroattenuation.<\/jats:p>","DOI":"10.1099\/vir.0.82935-0","type":"journal-article","created":{"date-parts":[[2007,8,13]],"date-time":"2007-08-13T19:28:15Z","timestamp":1187033295000},"page":"2533-2541","source":"Crossref","is-referenced-by-count":24,"title":["Functional consequences of attenuating mutations in the haemagglutinin\u2013neuraminidase, fusion and polymerase proteins of a wild-type mumps virus strain"],"prefix":"10.1099","volume":"88","author":[{"given":"Tahir","family":"Malik","sequence":"first","affiliation":[{"name":"DVP\/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candie","family":"Wolbert","sequence":"additional","affiliation":[{"name":"DVP\/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Mauldin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Sauder","sequence":"additional","affiliation":[{"name":"DVP\/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn M.","family":"Carbone","sequence":"additional","affiliation":[{"name":"DVP\/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Rubin","sequence":"additional","affiliation":[{"name":"DVP\/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1086\/517353","article-title":"Nucleotide sequence at position 1081 of the hemagglutinin-neuraminidase gene in the mumps Urabe vaccine strain","volume":"177","author":"Afzal","year":"1998","journal-title":"J Infect Dis"},{"key":"R2","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.1128\/JVI.80.10.4878-4889.2006","article-title":"N -glycans on Nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry","volume":"80","author":"Aguilar","year":"2006","journal-title":"J Virol"},{"key":"R3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1006\/viro.2001.1009","article-title":"Correlation of genetic variability with safety of mumps vaccine Urabe AM9 strain","volume":"287","author":"Amexis","year":"2001","journal-title":"Virology"},{"key":"R4","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/jmv.10392","article-title":"Identification of a new genotype H wild-type mumps virus strain and its molecular relatedness to other virulent and attenuated strains","volume":"70","author":"Amexis","year":"2003","journal-title":"J Med Virol"},{"key":"R5","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1042\/bj0810384","article-title":"Methods for the quantitative estimation of N -acetylneuraminic acid and their application to hydrolysates of sialomucoids","volume":"81","author":"Aminoff","year":"1961","journal-title":"Biochem J"},{"key":"R6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/tropej\/47.4.243","article-title":"Long-term neurological outcome of acute encephalitis","volume":"47","author":"Aygun","year":"2001","journal-title":"J Trop Pediatr"},{"key":"R7","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1006\/viro.1995.1251","article-title":"Individual roles of N -linked oligosaccharide chains in intracellular transport of the paramyxovirus SV5 fusion protein","volume":"209","author":"Bagai","year":"1995","journal-title":"Virology"},{"key":"R8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/nar\/25.1.217","article-title":"The PROSITE database, its status in 1997","volume":"25","author":"Bairoch","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"R9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.0954-6820.1943.tb09179.x","article-title":"Involvement of the central nervous system in mumps","volume":"113","author":"Bang","year":"1943","journal-title":"Acta Med Scand"},{"key":"R10","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1128\/JVI.76.14.7073-7081.2002","article-title":"Activity of polymerase proteins of vaccine and wild-type measles virus strains in a minigenome replication assay","volume":"76","author":"Bankamp","year":"2002","journal-title":"J Virol"},{"key":"R11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/ana.410160304","article-title":"Encephalitis and aseptic meningitis, Olmsted County","volume":"16","author":"Beghi","year":"1984","journal-title":"Epidemiology. Ann Neurol"},{"key":"R12","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/infdis\/174.3.619","article-title":"The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid 335 of the hemagglutinin-neuraminidase gene with one form associated with disease","volume":"174","author":"Brown","year":"1996","journal-title":"J Infect Dis"},{"key":"R13","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1128\/JVI.73.1.251-259.1999","article-title":"Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter","volume":"73","author":"Buchholz","year":"1999","journal-title":"J Virol"},{"key":"R14","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0736-4679(02)00758-8","article-title":"A fatal case of acute transverse myelitis associated with mumps","volume":"24","author":"Caksen","year":"2003","journal-title":"J Emerg Med"},{"key":"R15","first-page":"1527","article-title":"Mumps virus","volume-title":"In Fields Virology","author":"Carbone","year":"2007"},{"key":"R16","first-page":"366","article-title":"Centers for Disease Control and Prevention","volume":"55","year":"2006","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"R17","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1128\/JVI.74.10.4831-4838.2000","article-title":"Rescue of mumps virus from cDNA","volume":"74","author":"Clarke","year":"2000","journal-title":"J Virol"},{"key":"R18","first-page":"930","article-title":"Mumps-associated acute cerebellar ataxia","volume":"146","author":"Cohen","year":"1992","journal-title":"Am J Dis Child"},{"key":"R19","first-page":"1","article-title":"Reverse genetics of mononegavirales","volume":"283","author":"Conzelmann","year":"2004","journal-title":"Curr Top Microbiol Immunol"},{"key":"R20","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/81002","article-title":"Crystal structure of the multifunctional paramyxovirus hemagglutinin-neuraminidase","volume":"7","author":"Crennell","year":"2000","journal-title":"Nat Struct Biol"},{"key":"R21","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1099\/0022-1317-69-11-2893","article-title":"Molecular cloning and characterization of six genes, determination of gene order and intergenic sequences and leader sequence of mumps virus","volume":"69","author":"Elango","year":"1988","journal-title":"J Gen Virol"},{"key":"R22","first-page":"253","article-title":"Vaccine-related mumps meningitis \u2013 Canada","volume":"16","author":"Furesz","year":"1990","journal-title":"Can Dis Wkly Rep"},{"key":"R23","first-page":"3","article-title":"Mumps and mumps vaccine: a global review","volume":"77","author":"Galazka","year":"1999","journal-title":"Bull World Health Organ"},{"key":"R24","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1136\/bmj.330.7500.1132","article-title":"Mumps and the UK epidemic 2005","volume":"330","author":"Gupta","year":"2005","journal-title":"BMJ"},{"key":"R25","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1128\/JVI.65.9.4565-4572.1991","article-title":"Enzymatic activity of poliovirus RNA polymerase mutants with single amino acid changes in the conserved YGDD amino acid motif","volume":"65","author":"Jablonski","year":"1991","journal-title":"J Virol"},{"key":"R26","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0168-1702(90)90073-K","article-title":"Hemagglutinin-neuraminidase (HN) amino acid alterations in neutralization escape mutants of Kilham mumps virus","volume":"17","author":"Kovamees","year":"1990","journal-title":"Virus Res"},{"key":"R27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.abb.2003.09.037","article-title":"Six-helix bundle assembly and analysis of the central core of mumps virus fusion protein","volume":"421","author":"Liu","year":"2004","journal-title":"Arch Biochem Biophys"},{"key":"R28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1128\/JVI.53.1.67-74.1985","article-title":"Hemagglutinin-neuraminidase glycoprotein as a determinant of pathogenicity in mumps virus hamster encephalitis: analysis of mutants selected with monoclonal antibodies","volume":"53","author":"Love","year":"1985","journal-title":"J Virol"},{"key":"R29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1006\/viro.2001.0899","article-title":"Carbohydrate modifications of the NDV fusion protein heptad repeat domains influence maturation and fusion activity","volume":"283","author":"McGinnes","year":"2001","journal-title":"Virology"},{"key":"R30","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1099\/0022-1317-64-7-1457","article-title":"Biosynthesis of mumps virus F glycoprotein: non-fusing strains efficiently cleave the F glycoprotein precursor","volume":"64","author":"Merz","year":"1983","journal-title":"J Gen Virol"},{"key":"R31","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/0140-6736(93)91069-X","article-title":"Risk of aseptic meningitis after measles, mumps and rubella vaccine in UK children","volume":"341","author":"Miller","year":"1993","journal-title":"Lancet"},{"key":"R32","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1128\/JVI.78.13.7274-7278.2004","article-title":"Influence of N -glycans on processing and biological activity of the Nipah virus fusion protein","volume":"78","author":"Moll","year":"2004","journal-title":"J Virol"},{"key":"R33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/348091a0","article-title":"New mammalian expression vectors","volume":"348","author":"Moss","year":"1990","journal-title":"Nature"},{"key":"R34","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1099\/0022-1317-75-6-1345","article-title":"Rift Valley fever virus L segment: correction of the sequence and possible functional role of newly identified regions conserved in RNA-dependent polymerases","volume":"75","author":"Muller","year":"1994","journal-title":"J Gen Virol"},{"key":"R35","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0387-7604(12)80352-4","article-title":"Hydrocephalus due to acute aqueductal stenosis following mumps infection: report of a case and review of the literature","volume":"14","author":"Ogata","year":"1992","journal-title":"Brain Dev"},{"key":"R36","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/0042-6822(92)90555-4","article-title":"Molecular cloning and sequence analysis of the mumps virus gene encoding the L protein and the trailer sequence","volume":"188","author":"Okazaki","year":"1992","journal-title":"Virology"},{"key":"R37","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1128\/JVI.64.9.4137-4145.1990","article-title":"RNA editing by G-nucleotide insertion in mumps virus P-gene mRNA transcripts","volume":"64","author":"Paterson","year":"1990","journal-title":"J Virol"},{"key":"R38","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1001\/jama.284.20.2643","article-title":"Mumps and rubella eliminated from Finland","volume":"284","author":"Peltola","year":"2000","journal-title":"JAMA"},{"key":"R39","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1128\/JVI.77.7.4181-4190.2003","article-title":"Mutations in the putative HR-C region of the measles virus F2 glycoprotein modulate syncytium formation","volume":"77","author":"Plemper","year":"2003","journal-title":"J Virol"},{"key":"R40","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1371\/journal.pone.0000279","article-title":"Cytosolic 5\u2032-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response","volume":"2","author":"Plumet","year":"2007","journal-title":"PLoS ONE"},{"key":"R41","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1002\/j.1460-2075.1989.tb08565.x","article-title":"Identification of four conserved motifs among the RNA-dependent polymerase encoding elements","volume":"8","author":"Poch","year":"1989","journal-title":"EMBO J"},{"key":"R42","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1099\/0022-1317-71-5-1153","article-title":"Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: theoretical assignment of functional domains","volume":"71","author":"Poch","year":"1990","journal-title":"J Gen Virol"},{"key":"R43","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1099\/0022-1317-46-2-501","article-title":"Polypeptide synthesis in mumps virus-infected cells","volume":"46","author":"Rima","year":"1980","journal-title":"J Gen Virol"},{"key":"R44","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1055\/s-2000-9427","article-title":"Viral meningitis","volume":"20","author":"Rotbart","year":"2000","journal-title":"Semin Neurol"},{"key":"R45","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1128\/JVI.74.11.5382-5384.2000","article-title":"Evaluation of a neonatal rat model for prediction of mumps virus neurovirulence in humans","volume":"74","author":"Rubin","year":"2000","journal-title":"J Virol"},{"key":"R46","doi-asserted-by":"crossref","first-page":"11616","DOI":"10.1128\/JVI.77.21.11616-11624.2003","article-title":"Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype","volume":"77","author":"Rubin","year":"2003","journal-title":"J Virol"},{"key":"R47","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1086\/428098","article-title":"The rat-based neurovirulence safety test for the assessment of mumps virus neurovirulence in humans: an international collaborative study","volume":"191","author":"Rubin","year":"2005","journal-title":"J Infect Dis"},{"key":"R48","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1136\/bmj.330.7500.1119","article-title":"Mumps outbreaks across England and Wales in 2004: observational study","volume":"330","author":"Savage","year":"2005","journal-title":"BMJ"},{"key":"R49","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/oxfordjournals.jbchem.a022731","article-title":"Functional analysis of the individual oligosaccharide chains of Sendai virus fusion protein","volume":"128","author":"Segawa","year":"2000","journal-title":"J Biochem (Tokyo)"},{"key":"R50","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1006\/viro.1993.1180","article-title":"The attachment function of the Newcastle disease virus hemagglutinin-neuraminidase protein can be separated from fusion promotion by mutation","volume":"193","author":"Sergel","year":"1993","journal-title":"Virology"},{"key":"R51","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0042-6822(85)90279-X","article-title":"Purification and amino-terminal protein sequence analysis of the mumps virus fusion protein","volume":"144","author":"Server","year":"1985","journal-title":"Virology"},{"key":"R52","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1023\/A:1007663429371","article-title":"The control of mumps in Israel","volume":"15","author":"Slater","year":"1999","journal-title":"Eur J Epidemiol"},{"key":"R53","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1006\/viro.2002.1644","article-title":"Different substitutions at conserved amino acids in domains II and III in the Sendai L RNA polymerase protein inactivate viral RNA synthesis","volume":"304","author":"Smallwood","year":"2002","journal-title":"Virology"},{"key":"R54","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/00006454-199103000-00008","article-title":"Aseptic meningitis as a complication of mumps vaccination","volume":"10","author":"Sugiura","year":"1991","journal-title":"Pediatr Infect Dis J"},{"key":"R55","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0042-6822(92)90482-5","article-title":"Expression of mumps virus glycoproteins in mammalian cells from cloned cDNAs: both F and HN proteins are required for cell fusion","volume":"187","author":"Tanabayashi","year":"1992","journal-title":"Virology"},{"key":"R56","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1056\/NEJM197012312832707","article-title":"Aqueductal stenosis and hydrocephalus after mumps encephalitis","volume":"283","author":"Timmons","year":"1970","journal-title":"N Engl J Med"},{"key":"R57","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","article-title":"Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications","volume":"76","author":"Towbin","year":"1979","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R58","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1099\/0022-1317-67-10-2259","article-title":"Monoclonal antibodies against the glycoproteins of mumps virus: fusion inhibition by anti-HN monoclonal antibody","volume":"67","author":"Tsurudome","year":"1986","journal-title":"J Gen Virol"},{"key":"R59","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S0140-6736(95)92311-X","article-title":"Aseptic meningitis caused by measles-mumps-rubella vaccine in Japan","volume":"346","author":"Ueda","year":"1995","journal-title":"Lancet"},{"key":"R60","doi-asserted-by":"crossref","first-page":"10202","DOI":"10.1128\/JVI.77.19.10202-10212.2003","article-title":"N -linked glycans with similar location in the fusion protein head modulate paramyxovirus fusion","volume":"77","author":"von Messling","year":"2003","journal-title":"J Virol"},{"key":"R61","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1128\/JVI.78.15.7894-7903.2004","article-title":"Canine distemper virus and measles virus fusion glycoprotein trimers: partial membrane-proximal ectodomain cleavage enhances function","volume":"78","author":"von Messling","year":"2004","journal-title":"J Virol"},{"key":"R62","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0042-6822(87)90477-6","article-title":"Cloning and sequencing of the mumps virus fusion protein gene","volume":"159","author":"Waxham","year":"1987","journal-title":"Virology"},{"key":"R63","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1006\/viro.1995.1332","article-title":"Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells","volume":"210","author":"Wyatt","year":"1995","journal-title":"Virology"},{"key":"R64","doi-asserted-by":"crossref","first-page":"4744","DOI":"10.1128\/JVI.75.10.4744-4751.2001","article-title":"N -glycans of F protein differentially affect fusion activity of human respiratory syncytial virus","volume":"75","author":"Zimmer","year":"2001","journal-title":"J Virol"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.82935-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T21:49:29Z","timestamp":1603748969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.82935-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,1]]},"references-count":64,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2007,9,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.82935-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,1]]}}}