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Published online ahead of print on 12 March 2009 as doi:10.1099/vir.0.009449-0
Journal of General Virology 2009;90:1741.

A more recent version of this article appeared on July 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.009449-0
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Single amino acid changes in the mumps virus HN and L proteins are associated with neuroattenuation.

Tahir H. Malik1, Candie Wolbert, Laura Nerret, Christian Sauder and Steven Rubin

United States Food and Drug Administration

1 E-mail: tahir.malik{at}fda.hhs.gov

We previously reported three amino acid changes, one each in the fusion (Ala/Thr-91->Thr), hemagglutinin-neuraminidase (Ser-466->Asn), and polymerase (Ile-736->Val) proteins 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 we show that the single amino acid change in the hemagglutinin-neuraminidase protein and to a lesser extent, the change in the polymerase protein result in neuroattenuation, as assessed in rats. The combination of both amino acid changes neuroattenuated the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the fusion 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 supportive evidence for the role of the hemagglutinin-neuraminidase protein as a virulence factor and, to our knowledge, this is first report to associate an amino acid change in the polymerase protein with mumps virus neuroattenuation.

Received 11 December 2008; accepted 7 March 2009.




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