The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity

被引：25

作者：

Argyris, EG

Kulkosky, J

Meyer, ME

Xu, Y

Mukhtar, M

Pomerantz, RJ

Williams, KJ

机构：

[1] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med,Ctr Human Virol & Biodef, Div Infect Dis & Environm Med,Dorrance H Hamilton, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Jefferson Med Coll, Div Endocrinol Diabet & Metab Dis,Dept Med, Dorrance H Hamilton Labs,Ctr Human Virol & Biodef, Philadelphia, PA 19107 USA

来源：

VIROLOGY | 2004年 / 330卷 / 02期

关键词：

human immunodeficiency virus type 1; Tat; heparan sulfate proteoglycans; long terminal repeat;

D O I：

10.1016/j.virol.2004.10.011

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 I-125-labeled Tat with minimal lysosomal degradation. Pre-treatment of cells with heparitinase almost completely abolished I-125-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. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：481 / 486

页数：6

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