title: Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1.
abstract: 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 IC(50)s ranging from 0.1 to 7.4 μg/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.
authors.affiliation: Military HIV Research Program, Henry M. Jackson Foundation, Rockville, MD 20850, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosa Borges
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Benitra
authors.initials: B
authors.lastname: Johnson
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Benesi
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kensinger
authors.forename: Fred C
authors.initials: FC
authors.lastname: Krebs
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.forename: Robert
authors.initials: R
authors.lastname: Blumenthal
authors.forename: Anu
authors.initials: A
authors.lastname: Puri
authors.forename: Francine E
authors.initials: FE
authors.lastname: McCutchan
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Cara-Lynne
authors.initials: CL
authors.lastname: Schengrund
mesh_terms: D019380:Anti-HIV Agents; D002241:Carbohydrates / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D050091:Dendrimers; D015870:Gene Expression; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D053586:Virus Internalization
chemical_list: D019380:Anti-HIV Agents; D002241:Carbohydrates; D050091:Dendrimers