The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms

Monique V. Davies, Hwai Wen Chang, Bertram Jacobs, Randal J. Kaufman

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Abstract

Vaccinia virus has evolved multiple mechanisms to counteract the interferon-induced antiviral host cell response. Recently, two vaccinia virus gene products were shown to interfere with the activity of the double-stranded RNA-dependent protein kinase (PKR): the E3L gene product and the E3L gene product. We have evaluated the efficiency by which these gene products inhibit PKR and whether they act in a synergistic manner. The effects of the two vaccinia virus gene products were compared in an in vivo system in which translation of a reporter gene (dihydrofolate reductase or eukaryotic translation initiation factor 2α [eIF-2α]) was inhibited because of the localized activation of PKR. In this system, the E3L gene product, and to a lesser extent the K3L gene product, potentiated translation of the reporter gene and inhibited eIF-2α phosphorylation. Analysis in vitro demonstrated that the E3L gene product inhibited PKR approximately 50- to 100-fold more efficiently than the K3L gene product. However, further studies demonstrated that the mechanism of action of these two inhibitors was different. Whereas the E3L inhibitor interfered with the binding of the kinase to double-stranded RNA, the K3L inhibitor did not. We propose that the K3L inhibitor acts through its homology to eIF-2α to interfere with the interaction of eIF-2α with PKR. The two inhibitors did not display a synergistic effect on translation or eIF-2α phosphorylation. In addition, neither K3L nor E3L expression detectably altered cellular protein synthesis.

Original languageEnglish (US)
Pages (from-to)1688-1692
Number of pages5
JournalJournal of Virology
Volume67
Issue number3
StatePublished - Mar 1993
Externally publishedYes

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eIF-2 Kinase
Vaccinia virus
Double-Stranded RNA
double-stranded RNA
protein kinases
translation (genetics)
Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Genes
genes
Reporter Genes
reporter genes
phosphorylation
Phosphorylation
dihydrofolate reductase
Tetrahydrofolate Dehydrogenase
interferons
Interferons
Antiviral Agents
mechanism of action

ASJC Scopus subject areas

  • Immunology

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The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms. / Davies, Monique V.; Chang, Hwai Wen; Jacobs, Bertram; Kaufman, Randal J.

In: Journal of Virology, Vol. 67, No. 3, 03.1993, p. 1688-1692.

Research output: Contribution to journalArticle

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