Mycophenolic acid inhibits avian reovirus replication
Christopher M Robertson1, Laura L Hermann, Kevin M Coombs
1Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Abstract:
Avian reoviruses (ARV) are economically important pathogens, especially in the poultry industry, where they cause viral arthritis and tenosynovitis. Mycophenolic acid (MPA) is an inhibitor of inosine monophosphate dehydrogenase (mainly used clinically for immunosuppression) that inhibits the replication of several viruses. We demonstrate in this study that MPA also is capable of inhibiting ARV replication in QM5 quail fibrosarcoma cells. The selectivity index of MPA in QM5 cells was determined as approximately 41. Concentrations of > or =3 microg/ml MPA inhibited infectious ARV progeny production in QM5 cells by more than 100-fold. Inhibition of ARV replication also was seen in other cell lines, including HD-11 and Vero. Addition of exogenous guanosine to MPA-treated ARV-infected QM5 cells restored viral replicative capacity to nearly normal levels.
Insights
Mycophenolic acid (MPA) effectively inhibits avian reovirus (ARV) replication in cell cultures. Adding guanosine reversed this inhibition, suggesting a guanosine-dependent mechanism for ARV replication.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Avian reoviruses (ARV) are significant poultry pathogens causing viral arthritis and tenosynovitis.
- Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase inhibitor, is used clinically for immunosuppression and inhibits various viral replications.
Purpose of the Study:
- To investigate the potential of MPA as an antiviral agent against ARV.
- To determine the efficacy and mechanism of MPA's inhibition of ARV replication in cell culture.
Main Methods:
- ARV-infected QM5 quail fibrosarcoma cells were treated with MPA.
- Viral progeny production was quantified.
- ARV replication was assessed in HD-11 and Vero cell lines.
- The effect of exogenous guanosine addition was evaluated.
Main Results:
- MPA significantly inhibited ARV replication in QM5 cells, with a selectivity index of approximately 41.
- Concentrations of 3 microg/ml MPA reduced infectious ARV progeny by over 100-fold.
- MPA also inhibited ARV replication in HD-11 and Vero cells.
- Exogenous guanosine addition restored ARV replication in MPA-treated cells.
Conclusions:
- MPA demonstrates potent antiviral activity against ARV in cell culture.
- The mechanism of MPA's inhibition appears to be guanosine-dependent.
- MPA holds potential for controlling ARV infections in poultry.
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