3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

MULTIVALENT COMPOUNDS FUNCTIONALIZED WITH THE CARBOHYDRATE HEADGROUPS OF IMMUNE CELL-SURFACE GSLS AS INHIBITORS OF HIV-1 INFECTION.

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePp0104

Rosa Borges A.¹, Puri A.², Krebs F.C.³, Wigdahl B.³, Blumenthal R.², Rawat S.S.², Johnson B.T.², Schengrund C.-L.^1
1 Penn State University, College of Medicine, Hershey, Pennsylvania, United States of America, ² Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America, ³ Drexel University, College of Medicine, Philadelphia, Pennsylvania, United States of America

INTRODUCTION: In addition to CD4 and the chemokine coreceptors CCR5 and CXCR4, glycosphingolipids (GSLs) are needed for productive infection of cells by HIV-1. Since GSLs are often found localized in lipid rafts on the cell surface, their carbohydrate head groups are clustered together and may provide a platform for virus-cell surface interactions. Because protein-carbohydrate interactions often require multiple ligands, we hypothesized that multivalent carbohydrate molecules would inhibit viral infection of cells.

METHODS: Globotriose and 3'-sialyllactose were linked to dendrimer scaffolds. After linking each carbohydrate to different generations of dendrimers, MALDI-TOF MS was used to determine the average mass of each derivative. The mass was then used to calculate the average number of sugar units on each dendrimer. Using a live virus in vitro infection assay, the ability of each glycodendrimer to inhibit viral infection was compared to that of dextran sulfate. Cell viability studies were done to determine glycodendrimer toxicity

RESULTS: R5, X4, and X4R5 isolates showed varying levels of inhibition dependent on use of either globotriose- or 3'-sialyllactose-derivatized dendrimers. EC₅₀s of effective glycodendrimers ranged from sub-µM to sub-nM, values equivalent to, and sometimes better than, values obtained for dextran sulfate, a known inhibitor of viral infection. Cell viability studies indicated that none of the compounds were cytotoxic at concentrations less than 1 mg/ml.

CONCLUSIONS: The results show that multivalent carbohydrates carrying globotriose or 3'-sialyllactose moieties were effective inhibitors of HIV-1 infection of cells in vitro. More interestingly, inhibition of viral infection by our glycodendrimers suggests there may be a viral tropism dependence for cell-surface carbohydrates. These observations provide a novel approach for the design of new carbohydrate-based antiviral drugs. Based on their water-solubility, low cytotoxicity, and potent inhibition of cellular infection, these glycodendrimers merit consideration as prototypes for use in microbicide development, and possibly novel HIV-1 drug therapy.

Download PDF of this abstract.

050724
Basic | WePp0104 | Andrew Rosa Borges
New Antiretroviral Targets And Compounds

Copyright © 2005 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.