title: Single amino acid changes in the mumps virus haemagglutinin-neuraminidase and polymerase proteins are associated with neuroattenuation.
abstract: It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91-->Thr), haemagglutinin-neuraminidase (HN; Ser-466-->Asn) and polymerase (L; Ile-736-->Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the F protein, despite having a dramatic effect on protein function in vitro, was previously shown to not be involved in the observed neuroattenuation, highlighting the importance of conducting confirmatory in vivo studies. This report provides additional supporting evidence for the role of the HN protein as a virulence factor and, as far as is known, is the first report to associate an amino acid change in the L protein with mumps virus neuroattenuation.
authors.affiliation: DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Tahir H
authors.initials: TH
authors.lastname: Malik
authors.affiliation: DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Candie
authors.initials: C
authors.lastname: Wolbert
authors.affiliation: DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Nerret
authors.affiliation: DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Sauder
authors.affiliation: DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Rubin
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D015684:Gene Products, pol / Q000235:genetics / Q000502:physiology*; D015707:HN Protein / Q000235:genetics / Q000502:physiology*; D006849:Hydrocephalus / Q000473:pathology; D009109:Mumps virus / Q000235:genetics* / Q000472:pathogenicity*; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D051381:Rats; D012720:Severity of Illness Index; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D015684:Gene Products, pol; D015707:HN Protein; D037521:Virulence Factors