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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-10-19
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
323-35
pubmed:dateRevised
2008-11-21
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
pubmed:year
1995
pubmed:articleTitle
Differentiation of PC12 cells by infection with an HSV-1 vector expressing nerve growth factor.
pubmed:affiliation
Department of Pediatrics, University of California at San Diego, La Jolla 92093-0634, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't