| An altered and more efficient mechanism of CCR5 engagement contributes to macrophage tropism of CCR5-using HIV-1 envelopes. | |
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MedLine Citation:
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PMID: 20570309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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While CCR5 is the principal coreceptor used by macrophage (M)-tropic HIV-1, not all primary CCR5-using (R5) viruses enter macrophages efficiently. Here, we used functionally-diverse R5 envelope (Env) clones to characterize virus-cell interactions important for efficient CCR5-mediated macrophage entry. The magnitude of macrophage entry by Env-pseudotyped reporter viruses correlated with increased immunoreactivity of CD4-induced gp120 epitopes, increased ability to scavenge low levels of cell-surface CCR5, reduced sensitivity to the CCR5 inhibitor maraviroc, and increased dependence on specific residues in the CCR5 ECL2 region. These results are consistent with an altered and more efficient mechanism of CCR5 engagement. Structural studies revealed potential alterations within the gp120 V3 loop, the gp41 interaction sites at the gp120 C- and N-termini, and within the gp120 CD4 binding site which may directly or indirectly lead to more efficient CCR5-usage. Thus, enhanced gp120-CCR5 interactions may contribute to M-tropism of R5 HIV-1 strains through different structural mechanisms. |
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Authors:
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Jasminka Sterjovski; Michael Roche; Melissa J Churchill; Anne Ellett; William Farrugia; Lachlan R Gray; Daniel Cowley; Pantelis Poumbourios; Benhur Lee; Steven L Wesselingh; Anthony L Cunningham; Paul A Ramsland; Paul R Gorry |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-08 |
Journal Detail:
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Title: Virology Volume: 404 ISSN: 1096-0341 ISO Abbreviation: Virology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-08-09 Revised Date: 2012-04-30 |
Medline Journal Info:
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Nlm Unique ID: 0110674 Medline TA: Virology Country: United States |
Other Details:
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Languages: eng Pagination: 269-78 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Center for Virology, Burnet Institute, Melbourne, Victoria, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Cyclohexanes / pharmacology Dogs HIV Fusion Inhibitors / pharmacology HIV-1 / physiology* Humans Macrophages / metabolism, virology* Molecular Biology Protein Conformation Receptors, CCR5 / antagonists & inhibitors, drug effects, metabolism* Triazoles / pharmacology Virus Internalization* env Gene Products, Human Immunodeficiency Virus / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R21 AI092218/AI/NIAID NIH HHS; R21 AI092218-01/AI/NIAID NIH HHS; R21 AI092218-02/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclohexanes; 0/HIV Fusion Inhibitors; 0/Receptors, CCR5; 0/Triazoles; 0/env Gene Products, Human Immunodeficiency Virus; 0/maraviroc |
| Comments/Corrections | |
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