Defective translational control facilitates vesicular stomatitis virus oncolysis

Siddharth Balachandran, Glen N Barber

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Vesicular stomatitis virus (VSV) exerts potent antitumor activity, although the molecular mechanisms underlying its oncolytic properties remain to be fully clarified. Here, we demonstrate that normally resistant murine embryonic fibroblasts are rendered highly permissive to VSV replication following cellular transformation, a progression that appears to compromise the antiviral effects of interferon (IFN). Subsequent studies revealed normal dsRNA-dependent protein kinase (PKR) activation and phosphorylation of eukaryotic initiation factor 2 (eIF2) α. Nevertheless, eIF2B-mediated guanine nucleotide exchange activity downstream of eIF2 was frequently aberrant in transformed cells, neutralizing eIF2α phosphorylation and permitting VSV mRNA translation. Thus, defects in translational regulation can cooperate with impaired IFN signaling to facilitate VSV replication, and may represent a common hallmark of tumorigenesis.

Original languageEnglish
Pages (from-to)51-65
Number of pages15
JournalCancer Cell
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2004

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Vesicular Stomatitis
Eukaryotic Initiation Factor-2
Viruses
Virus Replication
Interferons
Phosphorylation
eIF-2 Kinase
Guanine Nucleotides
Protein Biosynthesis
Antiviral Agents
Carcinogenesis
Fibroblasts

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Defective translational control facilitates vesicular stomatitis virus oncolysis. / Balachandran, Siddharth; Barber, Glen N.

In: Cancer Cell, Vol. 5, No. 1, 01.01.2004, p. 51-65.

Research output: Contribution to journalArticle

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