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.
Argyris
Elias G
EG
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.
Kulkosky
Joseph
J
Meyer
Marie E
ME
Xu
Yan
Y
Mukhtar
Muhammad
M
Pomerantz
Roger J
RJ
Williams
Kevin Jon
KJ
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
D015696:Gene Products, tat; D019812:Heparan Sulfate Proteoglycans; D054322:tat Gene Products, Human Immunodeficiency Virus; C071927:perlecan; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase