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Obtaining a mumps virus with altered fidelity polymerase in order to reduce its virulence

Mumps virus is an RNA virus that causes respiratory infection usually associated with parotid glands swelling. In approximately 1-10% of cases infection can lead to occurence of encephalitis or meningitis due to highly neurotropic nature of the virus. All vaccines administrated against mumps are based on live attenuated strains. Some of them are not sufficiently attenuated while others are overly weakened or do not protect against currently circulating strains. One possibility for developing more efficient and safe vaccine could be altering viral population content due to the fact that viral population diversity is the main reason of severe virulence of RNA viruses. Identifying a high-fidelity polymerase by passaging virus in vitro with mutagens potentially results in decreased population diversity and attenuated phenotype. We applied this method on wild type mumps virus which was passaged over the course of 19 passages in A549 cells in the presence of ribavirin. Results obtained from three different passages unexpectedly show increase in the number of variants present in viral population. Understanding complexity of mumps virus variants, their selective fitness and impact on the host immune response will further help to determine if this approach can be used for design of new mumps vaccine.

mumps virus, viral population diversity, polymerase fidelity, ribavirin

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