Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1
- Military HIV Research Program, Henry M. Jackson Foundation, Rockville, MD 20850 (United States)
- Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD (United States)
- Department of Chemistry, Pennsylvania State University, State College, PA (United States)
- Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA (United States)
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA (United States)
- Military HIV Research Program, Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD (United States)
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{sub 50}s ranging from 0.1 to 7.4 {mu}g/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. -- Research Highlights: {yields}Multivalent carbohydrates (MVCs) inhibited infection of PBMCs by HIV-1. {yields}MVCs inhibited infection by T cell line-adapted viruses. {yields}MVCs inhibited infection by primary isolates of HIV-1. {yields}MVCs inhibited Env-mediated membrane fusion.
- OSTI ID:
- 21486909
- Journal Information:
- Virology, Vol. 408, Issue 1; Other Information: DOI: 10.1016/j.virol.2010.09.004; PII: S0042-6822(10)00579-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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