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

Dion Shah1, Silvia Vidal, Malen A Link

  • 1Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.

Journal of Medical Virology
|November 26, 2008
PubMed

Insights

Genetic changes in the mumps virus hemagglutinin-neuraminidase gene (HN) impact virulence. A specific HN mutation (lysine at position 335) is linked to vaccine-associated disease, while another (glutamic acid) shows attenuation.

Area of Science:

  • Virology
  • Vaccinology
  • Molecular Biology

Background:

  • Mumps virus vaccines are effective, but genetic determinants of reduced virulence are poorly understood.
  • The Urabe AM9 mumps vaccine was withdrawn due to insufficient attenuation and associated adverse events.
  • The Urabe AM9 vaccine contained a mixture of viruses differing in the hemagglutinin-neuraminidase (HN) gene sequence.

Purpose of the Study:

  • To investigate the genetic basis for differences in mumps virus virulence and attenuation.
  • To correlate specific genetic changes in the HN gene with mumps virus neurovirulence and vaccine-associated disease.

Main Methods:

  • Comparative sequencing of the hemagglutinin-neuraminidase (HN) gene from vaccine strains.
  • Utilizing a rat model to assess mumps virus neurovirulence.
  • Complete genome sequencing of attenuated and virulent mumps virus strains.

Main Results:

  • Viruses with lysine at HN amino acid position 335 were associated with post-vaccination meningitis.
  • Viruses with glutamic acid at HN position 335 were attenuated in a rat neurovirulence model.
  • Sixteen genetic differences were identified between attenuated and virulent strains, likely responsible for virulence variations and altered cell tropism.

Conclusions:

  • The amino acid at position 335 of the mumps virus HN protein is a key determinant of virulence.
  • Genetic variations identified contribute to differences in mumps virus neurovirulence and tropism.
  • Understanding these genetic changes is crucial for developing safer and more effective mumps vaccines.

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