Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy.
BACKGROUND
The green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells.


OBJECTIVE
To demonstrate that EGCG binds to the CD4 molecule at the gp120 attachment site and inhibits gp120 binding at physiologically relevant levels, thus establishing EGCG as a potential therapeutic treatment for HIV-1 infection.


METHODS
Nuclear magnetic resonance spectroscopy was used to examine the binding of EGCG and control, (-)-catechin, to CD4-IgG2 (PRO 542). Gp120 binding to human CD4+ T cells was analyzed by flow cytometry.


RESULTS
Addition of CD4 to EGCG produced a linear decrease in nuclear magnetic resonance signal intensity from EGCG but not from the control, (-)-catechin. In saturation transfer difference experiments, addition of 5.8 micromol/L CD4 to 310 micromol/L EGCG produced strong saturation at the aromatic rings of EGCG, but identical concentrations of (-)-catechin produced much smaller effects, implying EGCG/CD4 binding strong enough to reduce gp120/CD4 binding substantially. Molecular modeling studies suggested a binding site for EGCG in the D1 domain of CD4, the pocket that binds gp120. Physiologically relevant concentrations of EGCG (0.2 micromol/L) inhibited binding of gp120 to isolated human CD4+ T cells.


CONCLUSIONS
We have demonstrated clear evidence of high-affinity binding of EGCG to the CD4 molecule with a Kd of approximately 10 nmol/L and inhibition of gp120 binding to human CD4+ T cells.


CONCLUSIONS
Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.
Williamson
Mike P
MP
Department of Molecular Biology and Biotechnology, University of Sheffield, United Kingdom.
McCormick
Theron G
TG
Nance
Christina L
CL
Shearer
William T
WT
D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D016860:CD4 Immunoadhesins / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005419:Flavonoids; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010636:Phenols; D059808:Polyphenols; D011480:Protease Inhibitors / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D013662:Tea / Q000737:chemistry
D015704:CD4 Antigens; D016860:CD4 Immunoadhesins; C096753:CD4-IgG(2); D005419:Flavonoids; D015699:HIV Envelope Protein gp120; D010636:Phenols; D059808:Polyphenols; D011480:Protease Inhibitors; D015728:Receptors, HIV; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate