Research

Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

Michael J Bolton¹ and Robert F Garry^2*

• * Corresponding author: Robert F Garry rfgarry@tulane.edu

Author Affiliations

¹ Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center Division of Allergy and Infectious Diseases University of Washington 1100 Fairview Avenue Seattle, Washington 98109 USA

² Department of Microbiology and Immunology Tulane University 1430 Tulane Avenue New Orleans, Louisiana 70112 USA

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Virology Journal 2011, 8:45 doi:10.1186/1743-422X-8-45

Published: 31 January 2011

Abstract

Background

The surface glycoprotein (SU, gp120) of the human immunodeficiency virus (HIV) must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP) to bind the Duffy Antigen Receptor for Chemokines (DARC) and invade reticulocytes.

Results

Variable loop 3 (V3) of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins.

Conclusion

A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.