Assembly of the reovirus outer capsid requires μ1/σ3 interactions which are prevented by misfolded σ3 protein in temperature-sensitive mutant tsG453

Abstract

A temperature-sensitive reovirus mutant, tsG453, whose defect was mapped to major outer capsid protein σ3, makes core particles but fails to assemble the outer capsid around the core at non-permissive temperature. Previous studies that made use of electron cryo-microscopy and image reconstructions showed that μ1, the other major outer capsid protein, but not σ3, interact extensively with the core capsid. Although wild-type σ3 and μ1 interact with each other, immunocoprecipitation studies showed that mutant σ3 protein was incapable of interacting with μ1 at the non-permissive temperature. In addition, restrictively-grown mutant σ3 protein could not be precipitated by some σ3-specific monoclonal antibodies. These observations suggest that in a wild-type infection, specific σ3 and μ1 interactions result in changes in μ1 conformation which are required to allow μ1/σ3 complexes to condense onto the core capsid shell during outer capsid assembly, and that σ3 in non-permissive tsG453 infections is misfolded such that it cannot interact with μ1.