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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{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.

Authors:
;  [1];  [2];  [3];  [1];  [4]; ;  [5]; ;  [2];  [1]; ;  [6];  [4]
  1. Military HIV Research Program, Henry M. Jackson Foundation, Rockville, MD 20850 (United States)
  2. Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD (United States)
  3. Department of Chemistry, Pennsylvania State University, State College, PA (United States)
  4. Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA (United States)
  5. Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA (United States)
  6. Military HIV Research Program, Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD (United States)
Publication Date:
OSTI Identifier:
21486909
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 408; Journal 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.; Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; BLOOD; GLYCOPROTEINS; MEMBRANES; RECEPTORS; BIOLOGICAL MATERIALS; BODY FLUIDS; CARBOHYDRATES; MATERIALS; MEMBRANE PROTEINS; MICROORGANISMS; ORGANIC COMPOUNDS; PARASITES; PROTEINS; SACCHARIDES; VIRUSES

Citation Formats

Rosa Borges, Andrew, Wieczorek, Lindsay, Johnson, Benitra, Benesi, Alan J, Brown, Bruce K, Kensinger, Richard D, Krebs, Fred C, Wigdahl, Brian, Blumenthal, Robert, Puri, Anu, McCutchan, Francine E, Birx, Deborah L, Polonis, Victoria R, and Schengrund, Cara-Lynne. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1. United States: N. p., 2010. Web. doi:10.1016/j.virol.2010.09.004.
Rosa Borges, Andrew, Wieczorek, Lindsay, Johnson, Benitra, Benesi, Alan J, Brown, Bruce K, Kensinger, Richard D, Krebs, Fred C, Wigdahl, Brian, Blumenthal, Robert, Puri, Anu, McCutchan, Francine E, Birx, Deborah L, Polonis, Victoria R, & Schengrund, Cara-Lynne. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1. United States. https://doi.org/10.1016/j.virol.2010.09.004
Rosa Borges, Andrew, Wieczorek, Lindsay, Johnson, Benitra, Benesi, Alan J, Brown, Bruce K, Kensinger, Richard D, Krebs, Fred C, Wigdahl, Brian, Blumenthal, Robert, Puri, Anu, McCutchan, Francine E, Birx, Deborah L, Polonis, Victoria R, and Schengrund, Cara-Lynne. 2010. "Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1". United States. https://doi.org/10.1016/j.virol.2010.09.004.
@article{osti_21486909,
title = {Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1},
author = {Rosa Borges, Andrew and Wieczorek, Lindsay and Johnson, Benitra and Benesi, Alan J and Brown, Bruce K and Kensinger, Richard D and Krebs, Fred C and Wigdahl, Brian and Blumenthal, Robert and Puri, Anu and McCutchan, Francine E and Birx, Deborah L and Polonis, Victoria R and Schengrund, Cara-Lynne},
abstractNote = {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.},
doi = {10.1016/j.virol.2010.09.004},
url = {https://www.osti.gov/biblio/21486909}, journal = {Virology},
issn = {0042-6822},
number = 1,
volume = 408,
place = {United States},
year = {Sun Dec 05 00:00:00 EST 2010},
month = {Sun Dec 05 00:00:00 EST 2010}
}