He, Weijing and Neil, Stuart and Kulkarni, Hemant and Wright, Edward and Agan, Brian K. and Marconi, Vincent C. and Dolan, Matthew J. and Weiss, Robin A. and Ahuja, Sunil K. (2008) 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 and Microbe, 4 (1). pp. 52-62. ISSN 1931-3128
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Official URL: http://dx.doi.org/10.1016/j.chom.2008.06.002
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.
|Research Community:||University of Westminster > Life Sciences, School of|
|Deposited On:||04 Aug 2011 14:41|
|Last Modified:||04 Aug 2011 14:41|
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