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Journal of Virology, August 2007, p. 8293-8302, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00266-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The F Gene of Rodent Brain-Adapted Mumps Virus Is a Major Determinant of Neurovirulence{triangledown}

Ken Lemon,1 Bertus K. Rima,1 Stephen McQuaid,2 Ingrid V. Allen,1 and W. Paul Duprex1*

School of Biomedical Sciences, The Queen's University of Belfast, 97 Lisburn Road, Belfast, United Kingdom BT9 7BL,1 Neuropathology Laboratory, Royal Group of Hospitals Trust, Belfast, United Kingdom BT12 6BL2

Received 7 February 2007/ Accepted 26 March 2007

Prior to the introduction of live-attenuated vaccines, mumps virus (MuV) was the leading cause of virus-induced meningitis. Although vaccination has been effective at controlling the disease, the use of insufficiently attenuated strains has been associated with high rates of aseptic meningitis in vaccinees. The molecular basis of MuV attenuation is poorly understood, and no reliable molecular markers of virulence have been identified. In this study, reverse genetics has been used to identify molecular determinants of MuV neuropathogenesis. Recombinant viruses, containing the envelope-associated genes from the Kilham (MuVKH) rodent brain-adapted strain of MuV, were generated in the Jeryl Lynn 5 (MuVJL5) vaccine strain background. The syncytium phenotypes of the recombinant viruses on Vero cells differed depending on the source of the fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins, with heterologous combinations showing either an increase or a decrease in the level of cell fusion compared to that of the homologous parental combinations. This was confirmed by transiently cotransfecting eukaryotic F and HN glycoprotein expression constructs. A Lewis rat model that discriminates between neurovirulent and nonneurovirulent MuV strains based on the extent of hydrocephalus induced in the rat brain after intracerebral inoculation was used to assess the phenotype of the recombinant viruses. Expression of the matrix (M), small hydrophobic (SH), or HN gene in isolation did not confer a neurovirulent phenotype. Expression of the F gene of the neurovirulent strain alone was sufficient to induce significant levels of hydrocephalus. Coexpression of the homologous HN gene led to a marginal increase in the level of hydrocephalus.

* Corresponding author. Mailing address: School of Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL, Northern Ireland, United Kingdom. Phone: 44 28 9097 2060. Fax: 44 28 9097 5877. E-mail: p.duprex{at}qub.ac.uk

{triangledown} Published ahead of print on 2 May 2007.

Journal of Virology, August 2007, p. 8293-8302, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00266-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chambers, P., Rima, B. K., Duprex, W. P. (2009). Molecular differences between two Jeryl Lynn mumps virus vaccine component strains, JL5 and JL2. J. Gen. Virol. 90: 2973-2981 [Abstract] [Full Text]  
  • Xu, R., Nasar, F., Megati, S., Luckay, A., Lee, M., Udem, S. A., Eldridge, J. H., Egan, M. A., Emini, E., Clarke, D. K. (2009). Prime-Boost Vaccination with Recombinant Mumps Virus and Recombinant Vesicular Stomatitis Virus Vectors Elicits an Enhanced Human Immunodeficiency Virus Type 1 Gag-Specific Cellular Immune Response in Rhesus Macaques. J. Virol. 83: 9813-9823 [Abstract] [Full Text]  
  • Puri, M., Lemon, K., Duprex, W. P., Rima, B. K., Horvath, C. M. (2009). A Point Mutation, E95D, in the Mumps Virus V Protein Disengages STAT3 Targeting from STAT1 Targeting. J. Virol. 83: 6347-6356 [Abstract] [Full Text]  


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