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

Cell Host Microbe. 2008 Jul 17;4(1):52-62. doi: 10.1016/j.chom.2008.06.002.

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, approximately 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Africa
  • African Americans
  • Cells, Cultured
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Disease Progression
  • Disease Susceptibility*
  • Duffy Blood-Group System / biosynthesis*
  • Duffy Blood-Group System / genetics
  • Erythrocytes / virology*
  • Gene Frequency
  • Genotype
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Models, Biological
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Virus Attachment*

Substances

  • ACKR1 protein, human
  • Chemokines
  • Duffy Blood-Group System
  • Receptors, Cell Surface

Grant support