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Chimeric Sindbis-Ross River viruses to study interactions between alphavirus nonstructural and structural regions
R J Kuhn1, D E Griffin, K E Owen
1Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Journal of Virology
|November 1, 1996
Summary
Reciprocal alphavirus chimeras showed reduced replication, indicating essential interactions between structural and nonstructural proteins for efficient RNA synthesis and viral viability.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Sindbis virus and Ross River virus are alphaviruses with distinct but related protein sequences.
- Previous evidence suggests natural recombination can occur between alphaviruses, as seen with Western equine encephalitis virus.
Purpose of the Study:
- To investigate the functional compatibility of nonstructural and structural protein regions from different alphaviruses.
- To explore the impact of genomic region exchange on viral replication and RNA synthesis.
Main Methods:
- Generation of reciprocal Sindbis-Ross River chimeric viruses using full-length cDNA clones.
- Assessment of chimeric virus replication in various cell lines (mosquito, Vero) and infectivity in mice.
- Analysis of RNA synthesis to determine the cause of reduced replicative capacity.
Main Results:
- Both chimeric viruses replicated but showed reduced growth compared to parental viruses.
- The chimera with Sindbis nonstructural and Ross River structural proteins exhibited better growth than the reciprocal chimera.
- Reduced RNA synthesis in chimeras suggests suboptimal interactions between nonstructural and structural components.
Conclusions:
- Interactions between alphavirus nonstructural and structural proteins are crucial for efficient RNA replication.
- While most nonstructural/structural chimeras are viable, genomic interactions can limit their establishment.
- These findings provide insights into the constraints on natural alphavirus recombination.