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J Gen Virol 2007 Sep;88(Pt 9):2533-41

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

Malik T, Wolbert C, Mauldin J, Sauder C, Carbone KM, Rubin SA

Malik T (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bethesda, MD 20892 USA Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

Abstract

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-->Asp amino acid substitution at position 466 in the haemagglutinin-neuraminidase protein resulted in decreased receptor binding and neuraminidase activity, the Ala/Thr-->Thr selection in the fusion protein resulted in decreased fusion activity, and the Ile-->Val 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.


Category: Journal Article
PubMed ID: #17698664
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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