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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Myxoma virus M063R is a host range gene essential for virus replication in rabbit cells
John W Barrett1, Chew Shun Chang, Gen Wang
1The Biotherapeutics Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada N6G 2V4.
Abstract:
The myxoma virus M063R gene product exhibits some sequence similarity to the poxvirus host range gene, C7L, of vaccinia virus. To address the potential host range function of the M063R gene product in rabbits, a deletion mutant of myxoma virus (vMyx63KO) was generated and characterized. vMyx63KO replicated to normal titre levels and produced foci that were indistinguishable from those produced by MV in vitro in a monkey kidney cell line (BGMK) that are permissive for wild type MV. However, vMyx63KO failed to replicate in all rabbit cell lines tested, including both primary and established cells lines, as well as cells derived from a variety of tissues. M063R expression was not required for myxoma virus binding, entry or early gene expression, whereas DNA replication was aborted and late genes were not expressed in vMyx63KO infected rabbit cells. Thus, the replication block for vMyx63KO in rabbit cells preceded the stage of late gene expression and DNA replication. Finally, an in vivo pathogenesis study indicated that vMyx63KO failed to cause any signs of classic myxomatosis in infected rabbits, but functioned as a non-replicating vaccine and provided protection for subsequent challenge by wild type myxoma virus. Altogether, these observations demonstrate that M063R plays a critical role in determining the host specificity of myxoma virus in rabbit cells.
Insights
The myxoma virus M063R gene is essential for rabbit cell replication, acting as a key determinant of host specificity. Deleting this gene creates a safe vaccine candidate that protects rabbits from myxomatosis.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Myxoma virus (MV) is a significant pathogen causing lethal disease in rabbits.
- The M063R gene of MV shares sequence similarity with poxvirus host range genes, suggesting a role in host specificity.
Purpose of the Study:
- To investigate the function of the myxoma virus M063R gene in rabbit cells.
- To determine if M063R is essential for viral replication and pathogenesis in rabbits.
Main Methods:
- Generation and characterization of a M063R deletion mutant (vMyx63KO).
- In vitro replication assays in rabbit and monkey cell lines.
- In vivo pathogenesis studies in rabbits.
- Analysis of viral DNA replication and gene expression.
Main Results:
- vMyx63KO replicated normally in monkey cells but failed to replicate in rabbit cells.
- Replication block in rabbit cells occurred before DNA replication and late gene expression.
- vMyx63KO did not cause myxomatosis in rabbits but provided protection against wild-type MV challenge.
Conclusions:
- The M063R gene product is critical for myxoma virus replication in rabbit cells.
- M063R is a key determinant of myxoma virus host specificity.
- vMyx63KO represents a potential non-replicating vaccine for myxomatosis.
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