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Selection of mutants of mumps virus with altered structure and pathogenicity by passage in vivo
A Löve1, R Rydbeck, A Ljungdahl
1Department of Virology, Karolinska Institute, Stockholm, Sweden.
Abstract:
The neurotropic Kilham strain of mumps virus was serially passaged in newborn hamster brains in order to assess possible changes in viral characteristics. Two modes of passage were employed, one with a 4-5 day interval between inoculation and harvest and the other with a 10-12 day interval. After 10 and 8 passages, respectively, two viral variants were isolated which differed in antigen characteristics and in pathogenicity. In Vero cell cultures the variant derived from the short-term passage, designated as RK, showed much greater fusion capacity than the other, designated as SK. The highly fusing variant was highly lethal and caused much more extensive necrosis and grew to higher titers in the brain. With a series of monoclonal antibodies directed against the structural proteins of mumps virus marked differences between the variants could be detected in the nucleocapsid (NP) protein and also slight changes in the hemagglutinin-neuraminidase (HN) and phospho- (P) proteins. Differences were found in the preference of the viral variants to infect various regions of the brain. The RK variant heavily infected the caudate nucleus whereas the SK variant did not. This study demonstrates that different modes of passage can affect characteristics of virion components and disease pattern.
Insights
Serial passage of mumps virus in hamsters created two variants with distinct characteristics. Passage method influenced viral fusion, pathogenicity, and brain region targeting, highlighting adaptability.
Area of Science:
- Virology
- Neuroscience
- Pathology
Background:
- The Kilham strain of mumps virus is neurotropic.
- Serial passage in animal models is a common method to study viral evolution and adaptation.
Purpose of the Study:
- To investigate how serial passage in newborn hamster brains affects mumps virus characteristics.
- To identify and characterize distinct viral variants resulting from different passage intervals.
Main Methods:
- Serial intracerebral inoculation of newborn hamsters with the Kilham strain of mumps virus.
- Two passage intervals were used: short-term (4-5 days) and long-term (10-12 days).
- Viral variants were analyzed for antigenicity, pathogenicity, fusion capacity in Vero cells, and tropism in hamster brains using monoclonal antibodies.
Main Results:
- Two distinct mumps virus variants, RK (short-term passage) and SK (long-term passage), were isolated.
- The RK variant exhibited significantly higher fusion capacity, increased lethality, more extensive brain necrosis, and higher viral titers compared to the SK variant.
- Monoclonal antibody analysis revealed differences in nucleocapsid (NP) protein, and minor changes in hemagglutinin-neuraminidase (HN) and phospho- (P) proteins between variants.
- The RK variant showed a preference for infecting the caudate nucleus, while the SK variant did not.
Conclusions:
- Different serial passage modes can induce significant alterations in mumps virus characteristics.
- Viral passage strategies can influence viral pathogenicity, cell fusion activity, and tissue tropism.
- This study demonstrates the adaptability of mumps virus and provides insights into the generation of distinct viral variants with varying neurovirulence.