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

Weijing He, Stuart Neil, Hemant Kulkarni, Edward Wright, Brian K. Agan, Vincent C. Marconi, Matthew J. Dolan, Robin A. Weiss, Sunil K. Ahuja

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalCell Host and Microbe
Volume4
Issue number1
DOIs
StatePublished - Jul 17 2008

Keywords

  • HUMDISEASE
  • MICROBIO

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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