Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility.
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.
He
Weijing
W
Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
Neil
Stuart
S
Kulkarni
Hemant
H
Wright
Edward
E
Agan
Brian K
BK
Marconi
Vincent C
VC
Dolan
Matthew J
MJ
Weiss
Robin A
RA
Ahuja
Sunil K
SK
D000349:Africa; D001741:Black or African American; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004198:Disease Susceptibility; D004375:Duffy Blood-Group System / Q000096:biosynthesis* / Q000235:genetics; D004912:Erythrocytes / Q000821:virology*; D005787:Gene Frequency; D005838:Genotype; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008954:Models, Biological; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D053585:Virus Attachment
C473745:ACKR1 protein, human; D018925:Chemokines; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface