Preferential translation of reovirus mRNA by a σ3-dependent mechanism

Stephen Schmechel, Michael Chute, Pamela Skinner, Robert Anderson, Leslie Schiff

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52 Scopus citations

Abstract

We have characterized reovirus strains that differ in the degree to which they inhibit cellular protein synthesis and used them to investigate mechanisms regulating gene expression in infected cells. A previous genetic study associated distinct effects of reovirus strains on cellular translation with polymorphisms in viral protein σ3. In cell extracts, σ3 sequesters double-stranded RNA (dsRNA) and blocks activation of the dsRNA-activated protein kinase (PKR), an interferon-induced enzyme that inhibits translational initiation by phosphorylating eIF-2α. We found that in infected cells, cellular protein synthesis is translationally regulated in a strain-specific manner. Using immunoprecipitation and indirect immunofluorescence we showed that the effect of a strain on cellular translation is not determined by the level of σ3, but appears to result from differences in σ3 localization. In cells infected with a strain that spares cellular translation, σ3 is present throughout the cytoplasm, whereas in cells infected with inhibitory strains, σ3 is restricted to perinuclear viral factories. Biochemical studies suggested that diffuse localization of σ3 is a consequence of low affinity for capsid protein μ1. Our findings are consistent with a model in which the efficiency of cellular translation is determined by the cytoplasmic level of σ3 that is not complexed with μ1.

Original languageEnglish (US)
Pages (from-to)62-73
Number of pages12
JournalVirology
Volume232
Issue number1
DOIs
StatePublished - May 26 1997

Bibliographical note

Funding Information:
This work was supported by NIH Award R29AI32139 to L.S. S.S. was supported by MSTP Training Grant T32GM08244 and Microbiology/ Cancer Research Training Grant T32CA09138 from the NIH. We thank Zong Yu Chen, Kathleen Conklin, Chen Even, Eliane Meurs, Max Nibert, Stephen Rice, Deborah Shepard, and Peter Southern for helpful discussions, Brian Ruis for assistance with the phosphorimager, and Tim Leonard for assistance with photography.

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