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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1998-4-21
|
| pubmed:abstractText |
Monocytes and macrophages (Mo/Mphi) contribute to the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. A successful hematopoietic stem/progenitor cell (HSPC)-based gene therapy strategy for HIV-1 disease must protect Mo/Mphi as well as T cells from HIV-1-related pathology. In this report, we demonstrate that RevM10-transduced HSPCs isolated from cytokine-mobilized peripheral blood give rise to Mo/Mphi suppressing replication of Mphi-tropic HIV-1 isolates. A Moloney murine leukemia virus (MoMLV)-based retroviral vector encoding a bicistronic mRNA co-expressing RevM10 and the murine CD8alpha' chain (Lyt2) was used to transduce HSPCs. Following transduction, these cells were expanded and differentiated by short-term culture in methylcellulose containing various cytokines. In vitro differentiated Mo/Mphi were enriched by fluorescence activated cell sorting (FACS) for the co-expressed transgene (Lyt2) and myelomonocytic (CD33, CD14) surface markers. HIV-1 replication of two Mphi-tropic isolates (JR-FL, BaL) was inhibited in Mo/Mphi expressing RevM10 and Lyt2 relative to control cells expressing only Lyt2 but no functional RevM10 gene product. Cell proliferation and expression of lineage-specific surface markers was not altered in transduced, in vitro differentiated Mo/Mphi cells. This study supports the feasibility of HSPC-based gene therapy as a future treatment for HIV-1 disease.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
1043-0342
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
333-40
|
| pubmed:dateRevised |
2006-4-21
|
| pubmed:meshHeading |
pubmed-meshheading:9508051-Cell Transformation, Viral,
pubmed-meshheading:9508051-Genetic Vectors,
pubmed-meshheading:9508051-HIV-1,
pubmed-meshheading:9508051-Hematopoietic Stem Cells,
pubmed-meshheading:9508051-Humans,
pubmed-meshheading:9508051-Leukocytes, Mononuclear,
pubmed-meshheading:9508051-Macrophages,
pubmed-meshheading:9508051-Moloney murine leukemia virus,
pubmed-meshheading:9508051-Monocytes,
pubmed-meshheading:9508051-Virus Replication
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Inhibition of human immunodeficiency virus type 1 replication in myelomonocytic cells derived from retroviral vector-transduced peripheral blood progenitor cells.
|
| pubmed:affiliation |
Systemix, Inc., Palo Alto, CA 94304, USA.
|
| pubmed:publicationType |
Journal Article
|