Viral infection: 1. Regulation of protein synthesis during vaccinia viral infection of animal cells

Avirup Bose, Debabrata Saha, Naba K. Gupta

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Regulation of vaccinia vital infection was studied using three animal cell lines: KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (African green monkey kidney). KRC-7 is highly enriched in p67, a glycoprotein which protects eIF-2 α-subunit from phosphorylation by eIF-2 kinases. We report: (i) At 5 pfu per cell of the virus, KRC-7 is resistant to the virus. Other cells are sensitive. At 25 pfu per cell of the virus, KRC-7 is also sensitive to the virus. After productive vital infection, the cell extracts showed strong p67-DG activity and actively deglycosylated exogenous p67. After p67- deglycosylation, the cell extracts also phosphorylated eIF-2. (ii) The rate of synthesis of a major host protein (~45 kDa) in infected L929 cells measured after 2 h of vital infection declined more than 50%. The rate declined thereafter. The rate of synthesis of host proteins in viral- resistant KRC-7 cells (infected with 5 pfu per cell of the virus) remained unchanged. The mechanism of resistance of KRC7 cells to vacinia virus at 5 pfu per cell of the virus was investigated. The p67 level in these cells was varied by growing the cells under different physiological conditions such as serum starvation and expression of p67-sense and p67-antisense DNA. At low p67 level in the cells, p67-DG is activated. This deglycosylates p67 and inactivates p67. This accompanies eIF-2 phosphorylation and shutoff of host protein synthesis. At high p67 level in the cells, activation of p67-DG is prevented. This prevents shutoff of host protein synthesis and viral growth.

Original languageEnglish (US)
Pages (from-to)362-372
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume342
Issue number2
DOIs
StatePublished - Jun 15 1997

Keywords

  • Eukaryotic initiation factor 2
  • Viral infection
  • eIF-2 kinases
  • p67
  • p67-DG

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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