@article{15236fee4f49426aa38a19eb31dd0c63,
title = "Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility",
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.",
keywords = "HUMDISEASE, MICROBIO",
author = "Weijing He and Stuart Neil and Hemant Kulkarni and Edward Wright and Agan, {Brian K.} and Marconi, {Vincent C.} and Dolan, {Matthew J.} and Weiss, {Robin A.} and Ahuja, {Sunil K.}",
note = "Funding Information: We are indebted to the individuals who enrolled in these studies and who made this work possible. We thank S. Wegner and other members of the Infectious Disease Clinical Research Program (IDCRP) for critical support of this work; D. Kazandjian for helpful discussions; R. Sanchez, G. Cortez, V. Ann, B. Smith, and X. He for technical assistance; L. Song for graphic work; and A.S. Ahuja for forbearance. This work was supported by the Veterans Administration Center on AIDS and HIV Infection of the South Texas Veterans Health Care System and by a MERIT award (R37046326) and other awards (AI043279 and MH069270) from the NIH to S.K.A. S.K.A. is a recipient of the Elizabeth Glaser Scientist Award and the Burroughs Wellcome Clinical Scientist Award in Translational Research. Support for the WHMC cohort was provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS) of which the TriService AIDS Clinical Consortium (TACC) is a component. The IDCRP is a Department of Defense triservice program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine, in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011. This work was also supported by a grant from the UK Medical Research Council to R.A.W. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Departments of the Army, Navy, or Air Force, or the Department of Defense. The authors have no commercial or other association that might pose a conflict of interest. ",
year = "2008",
month = jul,
day = "17",
doi = "10.1016/j.chom.2008.06.002",
language = "English",
volume = "4",
pages = "52--62",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "1",
}