Identification of genetic mutations associated with attenuation and changes in tropism of Urabe mumps virus.

Although several effective mumps virus vaccines have been developed, almost nothing is known about the genetic changes responsible for loss of virulence. One vaccine, Urabe AM9, was withdrawn from the market because of insufficient attenuation. The vaccine was found to contain a mixture of viruses that could be distinguished based on the sequence of the hemagglutinin-neuraminidase gene (HN). Viruses containing lysine at HN amino acid position 335 were isolated from cases of post-vaccination parotitis or meningitis whereas viruses containing glutamic acid at this position were not associated with post-vaccination disease. Using a rat based model of mumps neurovirulence, we demonstrate that this latter virus is significantly attenuated compared to a virus isolated from a patient with post-vaccination meningitis. Complete sequence analysis of the genomes of the two viruses identified sixteen genetic differences, some or all of which must be responsible for differences in virulence. These same genetic differences also account for changes in tropism in cell culture.