Regulated expression of the interferon-induced protein kinase p68 (PKR) by vaccinia virus recombinants inhibits the replication of vesicular stomatitis virus but not that of poliovirus.
A direct antiviral role of the interferon-induced human protein kinase p68 has been shown only against encephalomyocarditis virus (EMCV) and vaccinia virus (VV). To determine if p68 kinase (PKR) has a broad antiviral effect, we have used coinfections between VV recombinants expressing p68 kinase under regulation of the lac I operator/repressor elements of Escherichia coli and two RNA viruses, vesicular stomatitis virus (VSV) and poliovirus. In cells coinfected with VV recombinants and VSV, induction with isopropyl-B-D-thiogalactoside (IPTG) of wild-type p68 kinase or a mutant lacking the dsRNA binding domain resulted in inhibition of both VV and VSV protein synthesis. This inhibition is not observed in cells infected with a catalytically inactive point mutant lys-arg296 of p68 kinase. When cells are coinfected with VV recombinants and poliovirus, induction of active p68 kinase resulted in a decrease in VV proteins but not in poliovirus proteins or poliovirus yields. Immunoblot analysis revealed that p68 kinase was expressed during mixed infections. Our results demonstrate a differential effect of p68 kinase on the replication of VV, VSV, and poliovirus. We suggest that in a particular virus-cell system, the different sensitivity of a virus to p68 kinase is probably due to levels of active enzyme.
Lee
S B
SB
Department of Biochemistry, State University of New York, Health Science Center at Brooklyn, USA.
Bablanian
R
R
Esteban
M
M
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D004790:Enzyme Induction; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000502:physiology*; D007739:L Cells; D051379:Mice; D017955:Poliovirus / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014616:Vaccinia virus / Q000235:genetics*; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*; D019892:eIF-2 Kinase
D000998:Antiviral Agents; D011994:Recombinant Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase