Binding of HTLV-1 virions to T cells occurs by a temperature and calcium-dependent process and is blocked by certain type 2 adenosine receptor antagonists.
A flow cytometric assay that measures binding of human T-lymphotropic virus type 1 (HTLV-1) virions to target cells was used to investigate the binding process and to screen for compounds affecting viral binding. Results showed that adenosine receptor type 2 antagonists effectively inhibit viral binding at concentrations below 10 microM; no inhibition was seen when antagonist was used to pretreat cells or was added post binding, suggesting direct interference with virus attachment. Efficient HTLV-1 binding required divalent calcium ions and temperatures greater than 20 degrees C. Disruption of lipid rafts by cholesterol depletion compromised viral binding but cleavage of glycosyl-phosphatidylinositol linkages had no effect. A monoclonal antibody (mAb) that recognizes HTLV-1 envelope positions 190-209 impaired binding of virus while other anti-envelope antibodies had no effect. These findings place major constraints on the nature of the HTLV-1 cell binding process and identify a class of inhibitors that may have potential for treatment of infection.
Hague
Bishop F
BF
Molecular and Cellular Immunogenetics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 50, Rm. 5515, 50 South Drive, Bethesda, MD 20892, USA. bhague@niaid.nih.gov
Zhao
Tong Mao
TM
Kindt
Thomas J
TJ
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000302:isolation & purification; D002461:Cell Line, Transformed; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D021962:Membrane Microdomains / Q000276:immunology / Q000821:virology; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011799:Quinazolines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D013816:Thermodynamics; D014230:Triazoles / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D011799:Quinazolines; D014230:Triazoles; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015762:2-Chloroadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine; D002118:Calcium; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine