Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1.
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.
Rosa Borges
Andrew
A
Military HIV Research Program, Henry M. Jackson Foundation, Rockville, MD 20850, USA.
Wieczorek
Lindsay
L
Johnson
Benitra
B
Benesi
Alan J
AJ
Brown
Bruce K
BK
Kensinger
Richard D
RD
Krebs
Fred C
FC
Wigdahl
Brian
B
Blumenthal
Robert
R
Puri
Anu
A
McCutchan
Francine E
FE
Birx
Deborah L
DL
Polonis
Victoria R
VR
Schengrund
Cara-Lynne
CL
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
D019380:Anti-HIV Agents; D002241:Carbohydrates; D050091:Dendrimers