TY - JOUR
T1 - Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1
AU - Rosa Borges, Andrew
AU - Wieczorek, Lindsay
AU - Johnson, Benitra
AU - Benesi, Alan J.
AU - Brown, Bruce K.
AU - Kensinger, Richard D.
AU - Krebs, Fred C.
AU - Wigdahl, Brian
AU - Blumenthal, Robert
AU - Puri, Anu
AU - McCutchan, Francine E.
AU - Birx, Deborah L.
AU - Polonis, Victoria R.
AU - Schengrund, Cara Lynne
N1 - Funding Information:
This work was supported in part by grant RO1 NS40231 from the National Institute of Allergy and Infectious Diseases (CLS), the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (AP and RB), and by Cooperative Agreement no. DAMD W81XWH-04-2-0005 between the U.S. Army Medical Research and Material Command and the Henry M. Jackson Foundation for the Advancement of Military Medicine, working with the Division of AIDS, National Institute for Allergy and Infectious Diseases, National Institutes of Health.
PY - 2010/12/5
Y1 - 2010/12/5
N2 - Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC50s ranging from 0.1 to 7.4μg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions.
AB - Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC50s ranging from 0.1 to 7.4μg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions.
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U2 - 10.1016/j.virol.2010.09.004
DO - 10.1016/j.virol.2010.09.004
M3 - Article
C2 - 20880566
AN - SCOPUS:78049264354
SN - 0042-6822
VL - 408
SP - 80
EP - 88
JO - Virology
JF - Virology
IS - 1
ER -