Document Detail


Long-term persistence of defective HSV-1 vectors in the rat brain is demonstrated by reactivation of vector gene expression.
MedLine Citation:
PMID:  8818649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Wild-type HSV-1 is known to persist indefinitely in neurons in the latent state; however, defective HSV-1 vectors, or amplicons, contain only approximately 1% of the HSV-1 genome and persistence of these HSV-1 vectors has not been studied even semiquantitatively in the adult rat brain. Defective HSV-1 vectors contain both an HSV-1 origin of replication and a packaging site, and in the presence of helper virus can undergo DNA replication and packaging into HSV-1 particles. Our prototype defective HSV-1 vector, pHSVlac, uses the HSV-1 immediate-early (IE) promoter to regulate expression of the Escherichia coli lacZ gene. Using cultured neuronal cells, we have previously shown that expression from pHSVlac can be augmented by superinfection with a helper virus. In this study, pHSVlac was delivered into the adult rat striatum or hippocampus, and 2-3 months after gene transfer we utilized superinfection with several replication-incompetent HSV-1 mutants to reactivate expression from pHSVlac in approximately 30% of the number of cells observed at 4 days after gene transfer. Thus, HSV-1 plasmid vectors can persist for at least 2-3 months in at least approximately 30% of the cells which are initially infected.
Authors:
P A Starr; F Lim; F D Grant; L Trask; P Lang; L Yu; A I Geller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gene therapy     Volume:  3     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-12-03     Completed Date:  1996-12-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  615-23     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Children's Hospital, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism,  pathology,  virology
Cell Line
Cercopithecus aethiops
Corpus Striatum / metabolism*,  pathology,  virology
Defective Viruses / genetics*,  physiology
Gene Expression
Genetic Vectors*
Herpesvirus 1, Human / genetics*,  physiology
Hippocampus / metabolism*,  pathology,  virology
Humans
Rats
Superinfection
Vero Cells
Virus Latency
Grant Support
ID/Acronym/Agency:
AG10827/AG/NIA NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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