Evidence that avian reovirus sigmaA protein is an inhibitor of the double-stranded RNA-dependent protein kinase.
J Gen Virol
; 84(Pt 6): 1629-1639, 2003 Jun.
Article
em En
| MEDLINE
| ID: mdl-12771434
ABSTRACT
The results of a previous study demonstrated that avian reovirus is highly resistant to the antiviral effects of interferon and suggested that the double-stranded RNA (dsRNA)-binding sigmaA protein might play an important role in that resistance. To gather more evidence on the interferon-inhibitory activity of sigmaA protein, its gene was cloned into the prokaryotic maltose-binding protein (MBP) gene fusion vector pMalC and into the recombinant vaccinia virus WRS2. The two recombinant sigmaA proteins displayed a dsRNA-binding affinity similar to that of sigmaA protein synthesized in avian reovirus-infected cells. Interestingly, MBP-sigmaA, but not MBP, was able to relieve the translation-inhibitory activity of dsRNA in reticulocyte lysates by blocking the activation of endogenous dsRNA-dependent enzymes. In addition, transient expression of sigmaA protein in HeLa cells rescued gene expression of a vaccinia virus mutant lacking the E3L gene, and insertion of the sigmaA-encoding gene into vaccinia virus conferred protection for the virus against interferon in chicken cells. Further studies demonstrated that expression of recombinant sigmaA in mammalian cells interfered with dsRNA-dependent protein kinase (PKR) function. From these results we conclude that sigmaA is capable of reversing the interferon-induced antiviral state by down-regulating PKR activity in a manner similar to other virus-encoded dsRNA-binding proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Core Viral
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Proteínas de Ligação a RNA
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EIF-2 Quinase
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Orthoreovirus Aviário
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article