Source:http://linkedlifedata.com/resource/pubmed/id/12726727
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-5-2
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pubmed:abstractText |
Sindbis virus (SIN) expression vectors offer the opportunity for studying neuropathogenesis because of their distinct neural cell tropism. Here, we demonstrate that a recombinant SIN vector expressing EGFP (SINrep5-EGFP) infected multiple cell types including neural cells from several species relevant to lentivirus pathogenesis with high levels of transgene expression. Infection of human neurons by a recombinant SIN (SINrep5-JRFL) expressing the full-length envelope from a neurovirulent human immunodeficiency virus type 1 (HIV-1) strain (JRFL) caused increased cytotoxicity compared to infection with SINrep5-EGFP (P < 0.001), while no cytotoxicity was observed among infected human astrocytes or monocytoid cells. Both human monocyte-derived macrophages (MDM) (P < 0.01) and astrocytes (P < 0.001) infected with SINrep5-JRFL released soluble neurotoxins in contrast to SINrep5-EGFP or mock-infected cells, although this was most prominent for the astrocytes. Implantation of SINrep5-JRFL into the brains of SCID/NOD mice induced neuroinflammation, neuronal loss, and neurobehavioral changes characteristic of HIV-1 infection, which were not present in SINrep5-EGFP or mock-infected animals. Thus SIN expression vectors represent novel tools for studying in vitro and in vivo HIV-1 neuropathogenesis because of their high levels of transgene expression in specific cell types within the brain.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0042-6822
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
309
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
61-74
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12726727-Animals,
pubmed-meshheading:12726727-Brain,
pubmed-meshheading:12726727-Gene Products, env,
pubmed-meshheading:12726727-Gene Transfer Techniques,
pubmed-meshheading:12726727-Genetic Vectors,
pubmed-meshheading:12726727-Green Fluorescent Proteins,
pubmed-meshheading:12726727-HIV-1,
pubmed-meshheading:12726727-Humans,
pubmed-meshheading:12726727-Luminescent Proteins,
pubmed-meshheading:12726727-Mice,
pubmed-meshheading:12726727-Neurons,
pubmed-meshheading:12726727-Rats,
pubmed-meshheading:12726727-Recombinant Proteins,
pubmed-meshheading:12726727-Sindbis Virus
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pubmed:year |
2003
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pubmed:articleTitle |
Human immunodeficiency virus type 1 envelope-mediated neuropathogenesis: targeted gene delivery by a Sindbis virus expression vector.
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pubmed:affiliation |
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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