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Human alpha-fetoprotein binds to primary macrophages.
Aurélie Atemezem1, Elisabeth Mbemba, Renée Marfaing
1UPRES 3410, Biothérapies, Bénéfices et Risques, UFR-SMBH, Université Paris XIII, Bobigny et Hôpital Jean Verdier, Bondy 93017, France.
Biochemical and Biophysical Research Communications
|August 15, 2002
Summary
Alpha-fetoprotein (AFP) binds directly to CCR5, a key receptor for HIV-1 entry into macrophages. This interaction explains how AFP inhibits R5-HIV-1 infection by blocking the virus
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Alpha-fetoprotein (AFP) is known to inhibit R5-HIV-1 infection of human monocyte-derived macrophages (MDM).
- A peptide mimicking the HIV-1 gp120 V3 domain (V3Cs) binds to the CCR5 receptor.
Purpose of the Study:
- To investigate the mechanism by which AFP inhibits R5-HIV-1 infection.
- To determine if AFP directly interacts with CCR5 on MDM.
Main Methods:
- Binding assays to quantify AFP interaction with MDM.
- Displacement assays using V3Cs peptide and MIP-1beta to assess competitive binding to CCR5.
- Experiments using CCR5-expressing and non-expressing HeLa cells to confirm CCR5 specificity.
Main Results:
- AFP binds to both high- and low-affinity sites on MDM.
- Heat denaturation and neuraminidase treatment of AFP reduce its binding to MDM.
- AFP displaces V3Cs binding, and MIP-1beta displaces AFP binding to MDM.
- AFP specifically binds to CCR5 expressed on MDM and HeLa cells.
Conclusions:
- AFP directly binds to CCR5 on human macrophages.
- This direct interaction between AFP and CCR5 is the mechanism underlying AFP's inhibition of R5-HIV-1 infection.