Defective translational control facilitates vesicular stomatitis virus oncolysis

Siddharth Balachandran; Glen N. Barber

doi:10.1016/S1535-6108(03)00330-1

Defective translational control facilitates vesicular stomatitis virus oncolysis

Siddharth Balachandran, Glen N. Barber

Cell Biology

Research output: Contribution to journal › Article › peer-review

152 Scopus citations

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 language	English (US)
Pages (from-to)	51-65
Number of pages	15
Journal	Cancer Cell
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/S1535-6108(03)00330-1
State	Published - Jan 2004

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

Access to Document

10.1016/S1535-6108(03)00330-1

Fingerprint Dive into the research topics of 'Defective translational control facilitates vesicular stomatitis virus oncolysis'. Together they form a unique fingerprint.

Cite this

@article{c6e7f8a9555b44399d4d1ae01206e0a6,

title = "Defective translational control facilitates vesicular stomatitis virus oncolysis",

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.",

author = "Siddharth Balachandran and Barber, {Glen N.}",

year = "2004",

month = jan,

doi = "10.1016/S1535-6108(03)00330-1",

language = "English (US)",

volume = "5",

pages = "51--65",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Defective translational control facilitates vesicular stomatitis virus oncolysis

AU - Balachandran, Siddharth

AU - Barber, Glen N.

PY - 2004/1

Y1 - 2004/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1642553650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642553650&partnerID=8YFLogxK

U2 - 10.1016/S1535-6108(03)00330-1

DO - 10.1016/S1535-6108(03)00330-1

M3 - Article

C2 - 14749126

AN - SCOPUS:1642553650

VL - 5

SP - 51

EP - 65

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 1

ER -

Defective translational control facilitates vesicular stomatitis virus oncolysis

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Cite this