Evidence that avian reovirus sigmaA protein is an inhibitor of the double-stranded RNA-dependent protein kinase

C. Gonzalez-Lopez
2003 Journal of General Virology  
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 sA protein might play an important role in that resistance. To gather more evidence on the interferon-inhibitory activity of sA 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 sA proteins
more » ... t sA proteins displayed a dsRNA-binding affinity similar to that of sA protein synthesized in avian reovirus-infected cells. Interestingly, MBP-sA, but not MBP, was able to relieve the translationinhibitory activity of dsRNA in reticulocyte lysates by blocking the activation of endogenous dsRNAdependent enzymes. In addition, transient expression of sA protein in HeLa cells rescued gene expression of a vaccinia virus mutant lacking the E3L gene, and insertion of the sA-encoding gene into vaccinia virus conferred protection for the virus against interferon in chicken cells. Further studies demonstrated that expression of recombinant sA in mammalian cells interfered with dsRNA-dependent protein kinase (PKR) function. From these results we conclude that sA 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.
doi:10.1099/vir.0.19004-0 pmid:12771434 fatcat:sehvp6luxjeutnibhmocnkqmce