THE MOLECULAR-BASIS OF VIRAL ONCOLYSIS - USURPATION OF THE RAS SIGNALING PATHWAY BY REOVIRUS

Citation
Je. Strong et al., THE MOLECULAR-BASIS OF VIRAL ONCOLYSIS - USURPATION OF THE RAS SIGNALING PATHWAY BY REOVIRUS, EMBO journal (Print), 17(12), 1998, pp. 3351-3362
Citations number
58
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
02614189
Volume
17
Issue
12
Year of publication
1998
Pages
3351 - 3362
Database
ISI
SICI code
0261-4189(1998)17:12<3351:TMOVO->2.0.ZU;2-X
Abstract
NIH-3T3 cells, which are resistant to reovirus infection, became susce ptible when transformed with activated Sos or Ras, Restriction of reov irus proliferation in untransformed NIH-3T3 cells was not at the level of viral gene transcription, but rather at the level of viral protein synthesis, An analysis of cell lysates revealed that a 65 kDa protein was phosphorylated in untransformed NIH-3T3 cells, but only after inf ection with reovirus, This protein was not phosphorylated in infected or uninfected transformed cells, The 65 M)a protein was determined to be the double-stranded RNA-activated protein kinase (PKR), whose phosp horylation leads to translation inhibition. Inhibition of PKR phosphor ylation by 2-aminopurine, or deletion of the Pkr gene, led to drastic enhancement of reovirus protein synthesis in untransformed cells, The emerging picture is one in which early viral transcripts trigger PKR p hosphorylation in untransformed cells, which in turn leads to inhibiti on of translation of viral genes; this phosphorylation event is blocke d by an element(s) in the Ras pathway in the transformed cells, allowi ng viral protein synthesis to ensue. The usurpation of the Ras signali ng pathway therefore constitutes the basis of reovirus oncolysis.