Human T-cell leukemia virus type 1 envelope glycoprotein gp46 interacts with cell surface heparan sulfate proteoglycans.
The major receptors required for attachment and entry of the human T-cell leukemia virus type 1 (HTLV-1) remain to be identified. Here we demonstrate that a functional, soluble form of the HTLV-1 surface envelope glycoprotein, gp46, fused to an immunoglobulin Fc region (gp46-Fc) binds to heparan sulfate proteoglycans (HSPGs) on mammalian cells. Substantial binding of gp46-Fc to HeLa and Chinese hamster ovary (CHO) K1 cells that express HSPGs was detected, whereas binding to the sister CHO lines 2244, which expresses no HSPGs, and 2241, which expresses no glycosaminoglycans (GAGs), was much reduced. Enzymatic removal of HSPGs from HeLa and CHO K1 cells also reduced gp46-Fc binding. Dextran sulfate inhibited gp46-Fc binding to HSPG-expressing cells in a dose-dependent manner, whereas chondroitin sulfate was less effective. By contrast, dextran sulfate inhibited gp46-Fc binding to GAG-negative cells such as CHO 2244, CHO 2241, and Jurkat T cells weakly or not at all. Dextran sulfate inhibited HTLV-1 envelope glycoprotein (Env)-pseudotyped virus infection of permissive, HSPG-expressing target cells and blocked syncytium formation between HTLV-1 Env-expressing cells and HSPG-expressing permissive target cells. Finally, HSPG-expressing cells were more permissive for HTLV-1 Env-pseudotyped virus infection than HSPG-negative cells. Thus, similar to other pathogenic viruses, HTLV-1 may have evolved to use HSPGs as cellular attachment receptors to facilitate its propagation.
Piñon
Josefina D
JD
Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee University, Dundee DD1 9SY, Scotland, United Kingdom.
Klasse
P J
PJ
Jassal
Sushma R
SR
Welson
Sandy
S
Weber
Jonathan
J
Brighty
David W
DW
Sattentau
Quentin J
QJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016264:Dextran Sulfate / Q000494:pharmacology; D015686:Gene Products, env / Q000378:metabolism*; D006367:HeLa Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D008561:Membrane Fusion; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D014158:Transcription, Genetic
D015686:Gene Products, env; D019812:Heparan Sulfate Proteoglycans; D007141:Immunoglobulin Fc Fragments; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I; D016264:Dextran Sulfate