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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-5-2
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
309
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Human immunodeficiency virus type 1 envelope-mediated neuropathogenesis: targeted gene delivery by a Sindbis virus expression vector.
pubmed:affiliation
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't