Mumps virus is member of the paramyxovirus family of viruses. The Urabe strain of mumps was attenuated to produce a vaccine that was introduced in several countries, but withdrawn from the market when it was discovered to be insufficiently attenuated. Two vaccine-associated Urabe viruses have been shown to have different tropisms in tissue culture. Gw7, isolated directly from the vaccine and which has been shown to be attenuated in an animal model, shows limited growth in human lung epithelial cells (A549) compared to monkey kidney cell line (Vero). 1004 10/2 is a virus isolated from a patient with post-vaccination meningitis caused by the Urabe vaccine and this virus grows to high titres in both A549 and Vero cells. A limited number of genetic differences between Gw7 and 1004 10/2 have been identified that must account for the growth differences in tissue culture. Using a combination of functional assays and genetic analysis of other Urabe viruses with growth patterns similar to Gw7 or 1004 10/2, it was demonstrated that the failure of Gw7 to replicate well in A549 cells is not due to differences in the sensitivity to interferon, differences in receptor binding, the M protein, or the SH protein. The results implicated the L protein. This was further supported by the observations of reduced protein synthesis and RNA synthesis in A549 cells compared to Vero cells. This suggested that genetic differences between the viruses caused differences in the function of the L protein during transcription of mRNA, which resulted in the observed tropisms.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/27727 |
| Date | January 2008 |
| Creators | Shah, Dion |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 125 p. |
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