Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region

Elena Dobrikova, Paola Florez, Shelton Bradrick, Matthias Gromeier

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3′ nontranslated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3′ terminus that control IRES-mediated gene expression and virus propagation.

Original languageEnglish (US)
Pages (from-to)15125-15130
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number25
DOIs
StatePublished - Dec 9 2003
Externally publishedYes

Fingerprint

Picornaviridae
Rhinovirus
Poliovirus
Viral Genome
Glioma
Viruses
Gene Expression
Neurons
Growth
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region. / Dobrikova, Elena; Florez, Paola; Bradrick, Shelton; Gromeier, Matthias.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 25, 09.12.2003, p. 15125-15130.

Research output: Contribution to journalArticle

@article{403345160766434e9fff699fbcb61566,
title = "Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region",
abstract = "We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3′ nontranslated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3′ terminus that control IRES-mediated gene expression and virus propagation.",
author = "Elena Dobrikova and Paola Florez and Shelton Bradrick and Matthias Gromeier",
year = "2003",
month = "12",
day = "9",
doi = "10.1073/pnas.2436464100",
language = "English (US)",
volume = "100",
pages = "15125--15130",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "25",

}

TY - JOUR

T1 - Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region

AU - Dobrikova, Elena

AU - Florez, Paola

AU - Bradrick, Shelton

AU - Gromeier, Matthias

PY - 2003/12/9

Y1 - 2003/12/9

N2 - We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3′ nontranslated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3′ terminus that control IRES-mediated gene expression and virus propagation.

AB - We have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (IRES) derived from human rhinovirus type 2. Insertion of the heterologous IRES causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. We now report the elucidation of a molecular mechanism responsible for the cell type-specific defect mediated by the rhinovirus IRES. Rhinovirus IRES function in neuronal cell types depends on specific structural elements within the 3′ nontranslated region of the viral genome. Our observations suggest long-range interactions between the IRES and the 3′ terminus that control IRES-mediated gene expression and virus propagation.

UR - http://www.scopus.com/inward/record.url?scp=0344303621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344303621&partnerID=8YFLogxK

U2 - 10.1073/pnas.2436464100

DO - 10.1073/pnas.2436464100

M3 - Article

C2 - 14645707

AN - SCOPUS:0344303621

VL - 100

SP - 15125

EP - 15130

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 25

ER -