Possible involvement of the double-stranded RNA-binding core protein sigmaA in the resistance of avian reovirus to interferon.
Treatment of primary cultures of chicken embryo fibroblasts with a recombinant chicken alpha/beta interferon (rcIFN) induces an antiviral state that causes a strong inhibition of vaccinia virus and vesicular stomatitis virus replication but has no effect on avian reovirus S1133 replication. The fact that avian reovirus polypeptides are synthesized normally in rcIFN-treated cells prompted us to investigate whether this virus expresses factors that interfere with the activation and/or the activity of the IFN-induced, double-stranded RNA (dsRNA)-dependent enzymes. Our results demonstrate that extracts of avian-reovirus-infected cells, but not those of uninfected cells, are able to relieve the translation-inhibitory activity of dsRNA in reticulocyte lysates, by blocking the activation of the dsRNA-dependent enzymes. In addition, our results show that protein sigmaA, an S1133 core polypeptide, binds to dsRNA in an irreversible manner and that clearing this protein from extracts of infected cells abolishes their protranslational capacity. Taken together, our results raise the interesting possibility that protein sigmaA antagonizes the IFN-induced cellular response against avian reovirus by blocking the intracellular activation of enzyme pathways dependent on dsRNA, as has been suggested for several other viral dsRNA-binding proteins.
Martínez-Costas
J
J
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, 15706-Santiago de Compostela (A Coruña), Spain.
González-López
C
C
Vakharia
V N
VN
Benavente
J
J
D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D007370:Interferon Type I / Q000494:pharmacology*; D018165:Orthoreovirus / Q000187:drug effects* / Q000502:physiology; D014176:Protein Biosynthesis; D012330:RNA, Double-Stranded / Q000378:metabolism* / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014758:Viral Core Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D007370:Interferon Type I; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins