Evidence that avian reovirus σA protein is an inhibitor of the double-stranded RNA-dependent protein kinase
González-López, Claudia and Martínez-Costas, José and Esteban, Mariano and Benavente, Javier,, 84, 1629-1639 (2003),
doi = https://doi.org/10.1099/vir.0.19004-0,
publicationName = Microbiology Society,
issn = 0022-1317,
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 σA protein might play an important role in that resistance. To gather more evidence on the interferon-inhibitory activity of σA 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 σA proteins displayed a dsRNA-binding affinity similar to that of σA protein synthesized in avian reovirus-infected cells. Interestingly, MBP–σA, 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 σA protein in HeLa cells rescued gene expression of a vaccinia virus mutant lacking the E3L gene, and insertion of the σA-encoding gene into vaccinia virus conferred protection for the virus against interferon in chicken cells. Further studies demonstrated that expression of recombinant σA in mammalian cells interfered with dsRNA-dependent protein kinase (PKR) function. From these results we conclude that σA 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.,
language=,
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