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.
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
Bishop F
BF
Hague
Tong Mao
TM
Zhao
Thomas J
TJ
Kindt
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