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Journal of Virology, October 1998, p. 8037-8042, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Comparison of the Neurovirulence of a Vaccine and a Wild-Type Mumps Virus Strain in the Developing Rat Brain

Steven A. Rubin,1 Mikhail Pletnikov,2 and Kathryn M. Carbone1,2,3,*

DVP/OVRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892,1 and Departments of Psychiatry2 and Medicine,3 Johns Hopkins University, Baltimore, Maryland 21205

Received 6 May 1998/Accepted 25 June 1998

Prior to the adoption of widespread vaccination programs, mumps virus was the leading cause of virus-induced central nervous system (CNS) disease. Mumps virus-associated CNS complications in vaccinees continue to be reported; outside the United States, some of these complications have been attributed to vaccination with insufficiently attenuated neurovirulent vaccine strains. The development of potentially neurovirulent, live, attenuated mumps virus vaccines stems largely from the lack of an animal model that can reliably predict the neurovirulence of mumps virus vaccine candidates in humans. The lack of an effective safety test with which to measure mumps virus neurovirulence has also hindered analysis of the neuropathogenesis of mumps virus infection and the identification of molecular determinants of neurovirulence. In this report we show, for the first time, that mumps virus infection of the neonatal rat leads to developmental abnormalities in the cerebellum due to cerebellar granule cell migration defects. The incidence of the cerebellar abnormalities and other neuropathological and clinical outcomes of mumps virus infection of the neonatal rat brain demonstrated the ability of this model to distinguish neurovirulent (Kilham) from nonneurovirulent (Jeryl Lynn) mumps virus strains. Thus, this neonatal rat model may prove useful in evaluating the neurovirulence potential of new live, attenuated vaccine strains and may also be of value in elucidating the molecular basis of mumps virus neurovirulence.

* Corresponding author. Mailing address: DVP/OVRR/CBER/FDA, Building 29A, Room 1A-21, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 827-1973. Fax: (301) 480-5679. E-mail: carbonek{at}a1.cber.fda.gov.

Journal of Virology, October 1998, p. 8037-8042, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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