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Nature Medicine  3, 1369 - 1375 (1997)

Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: Implications for HIV primary infection

Marina Zaitseva1, Andrew Blauvelt2, Shirley Lee1, Cheryl K. Lapham1, Vera Kiaus-Kovrun2, Howard Mostowski3, Jody Manischewitz1 & Hana Golding1, 4

  1Division of Viral Products Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Building 29B, Room 4NN04, HFM 454, 8800 Rockville Pike, Bethesda, Maryland 20892, USA

  2Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA

  3Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Building 29B, Room 4NN04, HFM 454, 8800 Rockville Pike, Bethesda, Maryland 20892, USA

  4Correspondence should be addressed to H.G.

Transmission of HIV-1 is predominantly restricted to macrophage (MPhi)-tropic strains. Langerhans ceils (LCs) in mucosal epithelium, as well as macrophages located in the submucosal tissues, may be initial targets for HIV-1. This study was designed to determine whether restricted transmission of HIV-1 correlates with expression and function of HIV-1 co-receptors on LCs and macrophages. Using polyclonal rabbit IgCs specific for the HIV co-receptors cytokines CXCR4 and CCR5, we found that freshly isolated epidermal LCs (resembling resident mucosal LCs) expressed CCR5, but not CXCR, on their surfaces. In concordance with surface expression, fresh LCs fused with Mphi -tropic but not with T-tropic HIV-1 envelopes. However, fresh LCs did contain intracellular CXCR4 protein that was transported to the surface during in vitro culture. Macrophages expressed high levels of both co-receptors on their surfaces, but only CCR5 was functional in a fusion assay. These data provide several possible explanations for the selective transmission of Mphi-tropic HIV variants and for the resistance to infection conferred by the CCR5 deletion.

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