Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth

Eliane F. Meurs, Yoshihiko Watanabe, Suzanne Kadereit, Glen N Barber, Michael G. Katze, Karen Chong, Bryan R G Williams, Ara G. Hovanessian

Research output: Contribution to journalArticle

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Abstract

The cDNA encoding interferon-induced buman double-stranded RNA-activaled p68 kinase was expressed in murine NIH 3T3 cells by using the pcDNA1/neo vector. Several stable clones were selected which expressed either the wild-type kinase or an inactive mutant possessing a single amino acid substitution in the invariant lysine 296 in the catalytic domain II, The transfected wild-type kinase showed properties similar to those of the natural kinase, such as subcellular ribosomal localization and dependence on double-stranded RNA for autophosphorytation. Upon infection with encephalomyocarditis virus (EMCV), wild-type- but not mutant-expressing clones were found to partially resist virus growth. Such natural antiviral activity was virus specific, since no inhibition was observed in the case of vesicular stomatitis virus infection. In accord with EMCV inhibition, the wild-type p68 kinase was found to be highly phosphorylated during infection. Furthermore, its natural substrate, the small subunit of protein synthesis initiation factor eIF2, was phosphorylated. These results demonstrate that p68 kinase is activated during EMCV infection, leading to reduced virus production.

Original languageEnglish
Pages (from-to)5805-5814
Number of pages10
JournalJournal of Virology
Volume66
Issue number10
StatePublished - Oct 1 1992
Externally publishedYes

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Eukaryotic Initiation Factor-2
Encephalomyocarditis virus
eIF-2 Kinase
Double-Stranded RNA
double-stranded RNA
phosphorylation
phosphotransferases (kinases)
Phosphotransferases
Phosphorylation
Virus Diseases
Viruses
mice
Growth
Clone Cells
NIH 3T3 Cells
Peptide Initiation Factors
Vesicular Stomatitis
Protein Subunits
cells
Amino Acid Substitution

ASJC Scopus subject areas

  • Immunology

Cite this

Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth. / Meurs, Eliane F.; Watanabe, Yoshihiko; Kadereit, Suzanne; Barber, Glen N; Katze, Michael G.; Chong, Karen; Williams, Bryan R G; Hovanessian, Ara G.

In: Journal of Virology, Vol. 66, No. 10, 01.10.1992, p. 5805-5814.

Research output: Contribution to journalArticle

Meurs, Eliane F. ; Watanabe, Yoshihiko ; Kadereit, Suzanne ; Barber, Glen N ; Katze, Michael G. ; Chong, Karen ; Williams, Bryan R G ; Hovanessian, Ara G. / Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth. In: Journal of Virology. 1992 ; Vol. 66, No. 10. pp. 5805-5814.
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