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Protein’s length, flexibility key to infection

Oct. 31, 2012, 8:00 AM

Reovirus sigma-1 protein structure. (courtesy of Dermody Lab)

Reoviruses – a family of viruses that infect most mammals – use a protein called sigma-1 to attach to host cells. Sigma-1 has an unusual long spike-like structure, which includes three domains separated by two flexible “linker” regions. How the conformation of sigma-1 contributes to reovirus infection is not understood.

Magda Bokiej and colleagues in the lab of Terence Dermody, M.D., the Dorothy Overall Wells Chair in Pediatrics, generated reoviruses with mutant sigma-1 molecules with altered lengths and flexibilities. They tested these mutant viruses for binding, internalization, uncoating, protein synthesis, and assembly. They found that sigma-1 length is important for reovirus binding to cells, linker region 1 plays a role in the incorporation of sigma-1 into new viral capsids, and linker region 2 participates in a post-uncoating replication step.

The findings, reported in the October Journal of Virology, show that the unique structural architecture of sigma-1 is required for efficient reovirus infection of host cells. Understanding how reoviruses bind and enter target cells is critical to efforts to develop reovirus for oncolytic and vaccine applications.

This research was supported by grants from the National Institute of General Medical Sciences (GM007347) and the National Institute of Allergy and Infectious Diseases (AI076983) of the National Institutes of Health, and by the Elizabeth B. Lamb Center for Pediatric Research.

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