The effect of the vaccinia K1 protein on the PKR-eIF2α pathway in RK13 and HeLa cells

Kristen L. Willis, Samir Patel, Yan Xiang, Joanna L. Shisler

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Activated PKR protein regulates downstream anti-viral effects, including inhibition of translation. Thus, many viruses encode proteins to inhibit PKR. Here, we provide evidence that the vaccinia virus K1 protein, a host-range protein, possesses this function. First, the expression of the wild-type K1 protein was necessary to inhibit virus-induced eIF2α phosphorylation, an indirect measure of PKR activation, in RK13 and HeLa cells. Second, virus-induced eIF2α phosphorylation no longer occurred in PKR-deficient HeLa cells, suggesting PKR was responsible for vaccinia virus-induced eIF2α modification. Third, in normal HeLa cells, K1 protein expression also prevented virus-mediated PKR phosphorylation (activation). Residues in the C-terminal portion of the ANK2 region of K1 were identified as necessary for this inhibitory phenotype. Interestingly, mutant viruses that failed to inhibit PKR activation, such as S2C#2, also did not replicate in HeLa cells, suggesting that K1's inhibition of PKR was required for a productive infection. In support of this theory, when PKR was absent from HeLa cells, there was a modest restoration of viral protein synthesis during S2C#2 infection. However, the increased protein synthesis was insufficient for a productive infection.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalVirology
Volume394
Issue number1
DOIs
StatePublished - Nov 10 2009

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Vaccinia
HeLa Cells
Viruses
Proteins
Vaccinia virus
Phosphorylation
Infection
Host Specificity
Viral Proteins
Phenotype

Keywords

  • eIF2α
  • Host range
  • K1L
  • PKR
  • Vaccinia

ASJC Scopus subject areas

  • Virology

Cite this

The effect of the vaccinia K1 protein on the PKR-eIF2α pathway in RK13 and HeLa cells. / Willis, Kristen L.; Patel, Samir; Xiang, Yan; Shisler, Joanna L.

In: Virology, Vol. 394, No. 1, 10.11.2009, p. 73-81.

Research output: Contribution to journalArticle

Willis, Kristen L. ; Patel, Samir ; Xiang, Yan ; Shisler, Joanna L. / The effect of the vaccinia K1 protein on the PKR-eIF2α pathway in RK13 and HeLa cells. In: Virology. 2009 ; Vol. 394, No. 1. pp. 73-81.
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