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Functional consequences of attenuating mutations in the haemagglutinin–neuraminidase, fusion and polymerase proteins of a wild-type mumps virus strain

¹ DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
² Department of Pharmacology, University of Virginia, Charlottesville, VA, USA

Correspondence
Tahir Malik
tahir.malik{at}fda.hhs.gov

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 SerAsp amino acid substitution at position 466 in the haemagglutinin–neuraminidase protein resulted in decreased receptor binding and neuraminidase activity, the Ala/ThrThr selection in the fusion protein resulted in decreased fusion activity, and the IleVal 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.

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				T. H. Malik, C. Wolbert, L. Nerret, C. Sauder, and S. Rubin Single amino acid changes in the mumps virus haemagglutinin-neuraminidase and polymerase proteins are associated with neuroattenuation J. Gen. Virol., July 1, 2009; 90(7): 1741 - 1747. [Abstract] [Full Text] [PDF]