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Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
CLINICAL IMPLICATIONS:
Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.
AuthorsMike P Williamson, Theron G McCormick, Christina L Nance, William T Shearer
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 118 Issue 6 Pg. 1369-74 (Dec 2006) ISSN: 0091-6749 [Print] United States
PMID17157668 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD4
  • CD4 Immunoadhesins
  • CD4-IgG(2)
  • Flavonoids
  • HIV Envelope Protein gp120
  • Phenols
  • Polyphenols
  • Protease Inhibitors
  • Receptors, HIV
  • Tea
  • Catechin
  • epigallocatechin gallate
Topics
  • Antigens, CD4 (metabolism)
  • Binding Sites
  • CD4 Immunoadhesins (metabolism)
  • Catechin (analogs & derivatives, chemistry, metabolism)
  • Flavonoids
  • HIV Envelope Protein gp120 (metabolism)
  • HIV Infections (drug therapy, immunology)
  • HIV-1
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Phenols
  • Polyphenols
  • Protease Inhibitors (metabolism)
  • Receptors, HIV (metabolism)
  • Tea (chemistry)

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