Document Detail

Attenuation of herpes simplex virus neurovirulence with picornavirus cis-acting genetic elements.
MedLine Citation:
PMID:  17079296     Owner:  NLM     Status:  MEDLINE    
Viral pathogenesis depends on a suitable milieu in target host cells permitting viral gene expression, propagation, and spread. In many instances, viral genomes can be manipulated to select for propagation in certain tissues or cell types. This has been achieved for the neurotropic poliovirus (PV) by exchange of the internal ribosomal entry site (IRES), which is responsible for translation of the uncapped plus-strand RNA genome. The IRES of human rhinovirus type 2 (HRV2) confers neuron-specific replication deficits to PV but has no effect on viral propagation in malignant glioma cells. We report here that placing the critical gamma(1)34.5 virulence genes of herpes simplex virus type 1 (HSV) under translation control of the HRV2 IRES results in neuroattenuation in mice. In contrast, IRES insertion permits HSV propagation in malignant glioma cell lines that do not support replication of HSV recombinants carrying gamma(1)34.5 deletions. Our observations indicate that the conditions for alternative translation initiation at the HRV2 IRES in malignant glioma cells differ from those in normal central nervous system (CNS) cells. Picornavirus regulatory sequences mediating cell type-specific gene expression in the CNS can be utilized to target cancerous cells at the level of translation regulation outside their natural context.
Stephanie A Campbell; Matthew Mulvey; Ian Mohr; Matthias Gromeier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-01
Journal Detail:
Title:  Journal of virology     Volume:  81     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-28     Completed Date:  2007-02-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  791-9     Citation Subset:  IM    
Division of Neurological Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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MeSH Terms
Brain / pathology,  virology*
Cell Line, Tumor
Central Nervous System Viral Diseases / pathology,  virology*
Cercopithecus aethiops
Gene Expression Regulation, Viral
Herpes Simplex / pathology,  virology*
Mice, Inbred BALB C
Recombination, Genetic
Rhinovirus / genetics*
Ribosomes / metabolism
Simplexvirus / genetics,  pathogenicity*,  physiology
Untranslated Regions*
Vero Cells
Viral Proteins / genetics,  metabolism*
Virus Replication
Grant Support
Reg. No./Substance:
0/Untranslated Regions; 0/Viral Proteins; 0/gamma 34.5 protein, Human herpesvirus 1

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