1887

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 A protein might play an important role in that resistance. To gather more evidence on the interferon-inhibitory activity of A 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 A proteins displayed a dsRNA-binding affinity similar to that of A protein synthesized in avian reovirus-infected cells. Interestingly, MBP–A, 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 A protein in HeLa cells rescued gene expression of a vaccinia virus mutant lacking the E3L gene, and insertion of the A-encoding gene into vaccinia virus conferred protection for the virus against interferon in chicken cells. Further studies demonstrated that expression of recombinant A in mammalian cells interfered with dsRNA-dependent protein kinase (PKR) function. From these results we conclude that A 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.

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2003-06-01
2020-01-18
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