Scientific Publications by FDA Staff

J Gen Virol 2009 Jul;90(Pt 7):1741-7

Single amino acid changes in the mumps virus HN and L proteins are associated with neuroattenuation.

Malik TH, Wolbert C, Nerret L, Sauder C, Rubin S

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.