Journal article
Specific Interactions between the Viral Coreceptor CXCR4 and the Biguanide-Based Compound NB325 Mediate Inhibition of Human Immunodeficiency Virus Type 1 Infection
Antimicrobial agents and chemotherapy, v 53(2), pp 631-638
Feb 2009
PMID: 19047650
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The present studies were conducted to better define the mechanism of action of polyethylene hexamethylene biguanide (PEHMB) (designated herein as NB325), which was shown in previous studies to inhibit infection by the human immunodeficiency virus type 1 (HIV-1). Fluorescence-activated flow cytometric analyses of activated human CD4
+
T lymphocytes exposed to NB325 demonstrated concentration-dependent reductions in CXCR4 epitope recognition in the absence of altered recognition of selected CD4 or CD3 epitopes. NB325 also inhibited chemotaxis of CD4
+
T lymphocytes induced by the CXCR4 ligand CXCL12. However, NB325 did not cause CXCR4 internalization (unlike CXCL12) and did not interfere with CXCL12 binding. Additional flow cytometric analyses using antibodies with distinct specificities for extracellular domains of CXCR4 demonstrated that NB325 specifically interfered with antibody binding to extracellular loop 2 (ECL2). This interaction was confirmed using competitive binding analyses, in which a peptide derived from CXCR4 ECL2 competitively inhibited NB325-mediated reductions in CXCR4 epitope recognition. Collectively, these results demonstrate that the biguanide-based compound NB325 inhibits HIV-1 infection by specifically interacting with the HIV-1 coreceptor CXCR4.
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Details
- Title
- Specific Interactions between the Viral Coreceptor CXCR4 and the Biguanide-Based Compound NB325 Mediate Inhibition of Human Immunodeficiency Virus Type 1 Infection
- Creators
- Nina Thakkar - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Vanessa Pirrone - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Shendra Passic - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Wei Zhu - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Vladyslav Kholodovych - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102William Welsh - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Robert F Rando - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Mohamed E Labib - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Brian Wigdahl - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Fred C Krebs - Department of Microbiology and Immunology, and Center for Molecular Therapeutics and Resistance, Center for Sexually Transmitted Disease, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
- Publication Details
- Antimicrobial agents and chemotherapy, v 53(2), pp 631-638
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000262646500036
- Scopus ID
- 2-s2.0-59749101058
- Other Identifier
- 991014877704404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy