Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility

Authors

Weijing He, South Texas Veterans Health Care System
Stuart Neil, University College London
Hemant Kulkarni, South Texas Veterans Health Care System
Edward Wright, University College London
Brian K. Agan, Uniformed Services University
Vincent C. Marconi, Uniformed Services University
Matthew J. Dolan, Uniformed Services University
Robin A. Weiss, University College London
Sunil K. Ahuja, South Texas Veterans Health Care System

Date of this Version

2008

Comments

Published in Cell Host & Microbe 4, 52–62, July 17, 2008.

Abstract

Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC -46C/C genotype, which confers a DARC negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC -46C/C is associated with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans, ~11% of the HIV-1 burden in Africa may be linked to this genotype. After infection occurs, however, DARC-negative RBC status is associated with slower disease progression. Furthermore, the disease-accelerating effect of a previously described CCL5 polymorphism is evident only in DARC-expressing and not in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation.