The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity
pmid: 15567441
The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity
Cell surface heparan sulfate proteoglycans (HSPGs) mediate internalization of HIV-1 Tat. Herein, we report that human WiDr cells, which express perlecan but no other HSPGs, can internalize 125I-labeled Tat with minimal lysosomal degradation. Pre-treatment of cells with heparitinase almost completely abolished 125I-Tat surface binding, while the use of an HIV-1 long terminal repeat (LTR) promoter-reporter construct demonstrated that transactivation was potently blocked by pretreatment of cells with heparitinase, indicating an essential role for perlecan in the biologic effects of Tat. We conclude that the perlecan mediates Tat uptake and is required for HIV-1 LTR-directed transactivation in this human cell type.
- Chestnut Hill College United States
- Thomas Jefferson University United States
Human immunodeficiency virus type I, Transcriptional Activation, Cell Line, Protein Transport, Long terminal repeat, Genes, Reporter, Virology, Gene Products, tat, HIV-1, Humans, tat Gene Products, Human Immunodeficiency Virus, Tat, Promoter Regions, Genetic, Heparan sulfate proteoglycans, Heparan Sulfate Proteoglycans, HIV Long Terminal Repeat, Polysaccharide-Lyases
Human immunodeficiency virus type I, Transcriptional Activation, Cell Line, Protein Transport, Long terminal repeat, Genes, Reporter, Virology, Gene Products, tat, HIV-1, Humans, tat Gene Products, Human Immunodeficiency Virus, Tat, Promoter Regions, Genetic, Heparan sulfate proteoglycans, Heparan Sulfate Proteoglycans, HIV Long Terminal Repeat, Polysaccharide-Lyases
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