title: The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity.
abstract: 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.
authors.affiliation: The Dorrance H. Hamilton Laboratories, Division of Infectious Diseases and Environmental Medicine, Center for Human Virology and Biodefense, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Elias G
authors.initials: EG
authors.lastname: Argyris
authors.forename: Joseph
authors.initials: J
authors.lastname: Kulkosky
authors.forename: Marie E
authors.initials: ME
authors.lastname: Meyer
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mukhtar
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: Kevin Jon
authors.initials: KJ
authors.lastname: Williams
mesh_terms: D002460:Cell Line; D015696:Gene Products, tat / Q000378:metabolism*; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D019812:Heparan Sulfate Proteoglycans; D054322:tat Gene Products, Human Immunodeficiency Virus; C071927:perlecan; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase