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Published on: November 1, 2011
Sequence polymorphisms in the reovirus σ1 attachment protein modulate encapsidation efficiency and replication in
Olivia L Welsh1,2, Alexa N Roth1,2, Danica M Sutherland1,2
1Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Higher amounts of the reovirus σ1 attachment protein in progeny virions enhance cell binding and viral spread in mice. This attachment protein encapsidation efficiency impacts viral replication in both cell cultures and animal models.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Viral attachment proteins are crucial for host cell interaction and viral replication.
- The biological significance of viral attachment protein encapsidation efficiency remains largely unexplored.
- Mammalian orthoreovirus (reovirus) σ1 protein is essential for attachment and its encapsidation efficiency varies among strains.
Purpose of the Study:
- To investigate the role of σ1 attachment protein encapsidation efficiency in viral replication.
- To engineer reovirus mutants with varying σ1 encapsidation efficiencies.
- To assess the impact of σ1 encapsidation on viral binding, replication, and dissemination in vitro and in vivo.
Main Methods:
- Engineered reovirus σ1 mutant viruses with substitutions at residues 22 and 249.
- Assessed σ1 encapsidation efficiency in progeny virions.
- Quantified viral binding to cells.
- Measured viral replication in cell culture and dissemination in mice.
Main Results:
- Substitutions at σ1 residues 22 and 249 altered σ1 encapsidation efficiency.
- Reoviruses with higher σ1 encapsidation bound cells more avidly.
- High σ1-encapsidating reoviruses showed enhanced replication in cell culture and more efficient dissemination in mice.
- Attachment protein capsid abundance influences viral replication.
Conclusions:
- σ1 attachment protein encapsidation efficiency is a critical factor in reovirus replication and pathogenesis.
- Increased σ1 abundance enhances viral binding, cell entry, and spread.
- Findings suggest potential for reovirus as an oncolytic therapeutic by manipulating σ1 encapsidation.
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