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Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype
Steven A Rubin1, Georgios Amexis, Mikhail Pletnikov
1DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. rubins@cber.fda.gov
Journal of Virology
|October 15, 2003
Summary
Researchers identified specific genetic changes in mumps virus responsible for its ability to infect the brain (neurotropism) and cause damage (neurovirulence). This study advances understanding of viral meningitis and informs vaccine development.
Area of Science:
- Virology
- Neuroscience
- Genetics
Background:
- Mumps virus is known for its neurotropism, causing viral meningitis before widespread vaccination.
- The genetic underpinnings of mumps virus neurovirulence and neurotropism remained unclear due to the absence of a suitable animal model.
Purpose of the Study:
- To investigate the genetic basis of mumps virus neurotropism and neurovirulence.
- To neuroadapt a vaccine strain and neuroattenuate a wild-type strain using cell culture passages.
- To identify specific viral genetic changes associated with altered neurovirulence.
Main Methods:
- Passaging mumps virus strains (Jeryl Lynn vaccine and 88-1961 wild type) in human neural and chicken fibroblast cells.
- Assessing neurovirulence and neurotropism in a rat model.
- Sequencing the complete genomes of parental strains and their variants.
Main Results:
- A neuroadapted Jeryl Lynn variant showed increased brain replication and damage.
- A neuroattenuated 88-1961 variant exhibited decreased neurotropic and neurovirulent properties.
- Specific amino acid changes in viral proteins (nucleoprotein, matrix, polymerase, fusion, hemagglutinin-neuraminidase) correlated with altered neurovirulence.
Conclusions:
- The study successfully generated mumps virus variants with modified neurovirulence.
- Key amino acid substitutions in specific viral proteins are linked to mumps virus neurotropism and neurovirulence.
- Findings provide insights into the molecular mechanisms of mumps virus central nervous system infections.