Source:http://linkedlifedata.com/resource/pubmed/id/11313818
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2001-4-23
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pubmed:abstractText |
CXCR4 is the major co-receptor used by X4 strains of human immunodeficiency virus type I (HIV-1). In HIV-1-infected patients, the appearance of X4 strains (T cell line-tropic) correlates with disease progression. Since its discovery, the CXCR4 co-receptor has been a major target for different agents which block its function, such as stromal-derived factor 1alpha (SDF-1alpha) and the anti-CXCR4 monoclonal antibody, 12G5. In the present studies, the 12G5 hybridoma was used to construct a single-chain variable antibody fragment (SFv). Murine leukemia virus (MLV) and simian virus 40 (SV(40)) were utilized as delivery vehicles for the anti-CXCR4 SFv. Intracellular expression of the anti-CXCR4 SFv led to down-regulation of this critical co-receptor, as demonstrated by immunostaining. This effect significantly and specifically protected transduced cells from challenge with HIV-1, as measured by HIV-1 p24 antigen expression. Inhibition of HIV-1 replication was specific for X4 HIV-1 strains as demonstrated by MAGI assays. HeLa-CD4/betagal-CCR5 cells expressing the anti-CXCR4 SFv showed significant inhibition of infectivity by the X4 HIV-1 strain NL4-3, but not with the R5 HIV-1 strain Bal. Thus, this anti-HIV-1 molecular therapy has the potential to inhibit HIV-1 replication and virion spread. Targeting CXCR4 by intracellular immunization could be of additional benefit to certain HIV-1-infected patients on highly active antiretroviral therapy (HAART).
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pubmed:grant | |
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 |
Mar
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pubmed:issn |
0969-7128
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
408-18
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11313818-Animals,
pubmed-meshheading:11313818-Cell Line,
pubmed-meshheading:11313818-Down-Regulation,
pubmed-meshheading:11313818-Gene Therapy,
pubmed-meshheading:11313818-Genetic Vectors,
pubmed-meshheading:11313818-HIV Infections,
pubmed-meshheading:11313818-HIV-1,
pubmed-meshheading:11313818-Humans,
pubmed-meshheading:11313818-Immunoglobulin Variable Region,
pubmed-meshheading:11313818-Leukemia Virus, Murine,
pubmed-meshheading:11313818-Receptors, CXCR4,
pubmed-meshheading:11313818-Simian virus 40,
pubmed-meshheading:11313818-T-Lymphocytes,
pubmed-meshheading:11313818-Virus Replication
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pubmed:year |
2001
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pubmed:articleTitle |
Inhibition of HIV-1 infection by down-regulation of the CXCR4 co-receptor using an intracellular single chain variable fragment against CXCR4.
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pubmed:affiliation |
The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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