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Activation of the alternative complement pathway by mumps infected cells: relationship to viral neuraminidase
Abstract:
An inverse relationship exists between the sialic acid content of a particle and its ability to activate the alternative complement pathway. The present studies were performed to determine if the neuraminidase (NANase) activities of different mumps virus strains could influence the ability of mumps virus infected cells to activate the alternative pathway. CV-1 cells were infected with three different mumps virus strains (RW, O'Take, and Kilham) and after 24 hours, 10 percent guinea pig serum (GPS) treated with EGTA/MgCl2 or GPS lacking the 4th component of complement (C4DGPS) was added to the cell monolayers. After 30 minutes, the percentage C3 consumed was determined by a functional hemolytic assay. Cells infected with RW (high NANase) consumed significantly more C3 (23.2 per cent) than cells infected with Kilham (5.7 percent, low NANase). Cells infected with O'Take were intermediate in their ability to activate C3. The degree of C3 deposition on the surface of infected cells, detected by fluorescence microscopy, was also greater for cells infected with the RW than the Kilham strain of mumps virus. These studies suggest that the NANase activity of mumps virus can influence the ability of infected cells to activate the alternative pathway and thereby, the ability of complement to participate in host defense against mumps virus infection.
Insights
Mumps virus neuraminidase (NANase) activity impacts complement activation. High NANase mumps virus strains enhance C3 consumption and deposition on infected cells, suggesting a role in host defense.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Sialic acid content inversely correlates with alternative complement pathway activation.
- Neuraminidase (NANase) is a key enzyme in viral replication and host cell interaction.
- The role of mumps virus NANase activity in complement activation remains unclear.
Purpose of the Study:
- To investigate the influence of mumps virus neuraminidase (NANase) activity on alternative complement pathway activation.
- To determine if different mumps virus strains with varying NANase levels differentially activate complement.
- To elucidate the mechanism by which mumps virus modulates host defense via complement.
Main Methods:
- Infection of CV-1 cells with three mumps virus strains (RW, O'Take, Kilham) with differing NANase activities.
- Incubation with complement-sufficient or deficient guinea pig serum (GPS).
- Quantification of C3 consumption using a hemolytic assay and C3 deposition via fluorescence microscopy.
Main Results:
- Cells infected with high NANase RW strain consumed significantly more C3 (23.2%) compared to low NANase Kilham strain (5.7%).
- O'Take strain showed intermediate C3 consumption.
- Increased C3 deposition was observed on cells infected with the RW strain versus the Kilham strain.
Conclusions:
- Mumps virus NANase activity directly influences the ability of infected cells to activate the alternative complement pathway.
- This modulation of complement activation by NANase may play a role in host defense against mumps virus.
- Understanding this interaction can inform strategies for managing mumps virus infections.