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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1995-10-19
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pubmed:abstractText |
We have developed an HSV-1 vector with mutations in the viral IE 3 and VP16 genes that expresses mouse beta nerve growth factor (NGF) from a latency associated transcript (LAT) promoter modified by insertion of a Rous sarcoma virus (RSV) enhancer. The backbone double mutant vector has reduced cytotoxicity compared with a single mutant deleted for IE 3 and is able to express the reporter luciferase gene in rat pheochromocytoma (PC12) cells at low but relatively stable levels in vitro. Intracellular NGF levels of approximately 3 pg per mg of cellular protein were detected in infected PC12 cells for at least 7 days after infection. Furthermore, infected PC12 cells exhibited differentiated morphology marked by neurite outgrowth similar to that found after exposure of PC12 cells to purified 2.5S beta NGF. A persistent level of 0.2 to 0.3 pM of the expressed NGF was detected in the culture media. The NGF-expressing vector also showed reduced cytotoxicity compared with that of the parental virus in infected PC12 cells. In PC12 cells that overexpress the human proto-oncogene bcl-2, the cytotoxicity of both viruses was significantly reduced. These studies demonstrate that the reduced cytotoxicity of the IE 3-VP16 double mutant virus and the increased duration of transgene expression from the RSV-modified LAT promoter permit terminal differentiation of PC12 cells after infection with an NGF-expressing HSV-1 vector.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0969-7128
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
323-35
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7671108-Animals,
pubmed-meshheading:7671108-Avian Sarcoma Viruses,
pubmed-meshheading:7671108-Base Sequence,
pubmed-meshheading:7671108-Cell Differentiation,
pubmed-meshheading:7671108-Cell Survival,
pubmed-meshheading:7671108-DNA, Complementary,
pubmed-meshheading:7671108-Enhancer Elements, Genetic,
pubmed-meshheading:7671108-Genes, Reporter,
pubmed-meshheading:7671108-Genetic Vectors,
pubmed-meshheading:7671108-Herpesvirus 1, Human,
pubmed-meshheading:7671108-Humans,
pubmed-meshheading:7671108-Luciferases,
pubmed-meshheading:7671108-Molecular Sequence Data,
pubmed-meshheading:7671108-Nerve Growth Factors,
pubmed-meshheading:7671108-PC12 Cells,
pubmed-meshheading:7671108-Promoter Regions, Genetic,
pubmed-meshheading:7671108-Proto-Oncogene Proteins,
pubmed-meshheading:7671108-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:7671108-Rats
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pubmed:year |
1995
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pubmed:articleTitle |
Differentiation of PC12 cells by infection with an HSV-1 vector expressing nerve growth factor.
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pubmed:affiliation |
Department of Pediatrics, University of California at San Diego, La Jolla 92093-0634, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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