| Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin. | |
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MedLine Citation:
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PMID: 21035429 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MBL structurally contains a type II-like collagenous domain and a carbohydrate recognition domain (CRD). We have recently generated three novel recombinant chimeric lectins (RCL), in which varying length of collagenous domain of mannose-binding lectin (MBL) is replaced with that of L-ficolin (L-FCN). CRD of MBL is used for target recognition because it has a broad spectrum in pathogen recognition compared with L-FCN. Results of our study demonstrate that these RCLs are potent inhibitors of influenza A virus (IAV). RCLs, against IAV, show dose-dependent activation of the lectin complement pathway, which is significantly higher than that of recombinant human MBL (rMBL). This activity is observed even without MBL-associated serine proteases (MASPs, provided by MBL deficient mouse sera), which have been thought to mediate complement activation. These observations suggest that RCLs are more efficient in associating with MASP-2, which predominantly mediates the activity. Yet, additional serum further increases the activity while RCL-mediated coagulation-like enzyme activities are diminished compared with rMBL, suggesting reduced association with MASP-1, which has been shown to mediate coagulation-like activity. These data suggest that RCLs may interfere less with host coagulation, which is advantageous to be a therapeutic drug. Importantly, these RCLs have surpassed rMBL for anti-viral activities, such as viral aggregation, reduction of viral hemagglutination (HA) and inhibition of virus-mediated HA and neuraminidase (NA) activities. These results are encouraging that novel RCLs could be used as anti-IAV agents with less side effect and that RCLs would be suitable candidates in developing a new anti-IAV therapy. |
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Authors:
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Wei-Chuan Chang; Kevan L Hartshorn; Mitchell R White; Patience Moyo; Ian C Michelow; Henry Koziel; Bernard T Kinane; Emmett V Schmidt; Teizo Fujita; Kazue Takahashi |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2010-10-28 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 81 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-12-27 Completed Date: 2011-01-21 Revised Date: 2013-01-16 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 388-95 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antiviral Agents / chemistry, pharmacology* Complement Activation Complement Pathway, Mannose-Binding Lectin / drug effects Dose-Response Relationship, Drug Hemagglutination, Viral / drug effects Influenza A virus / chemistry, drug effects* Lectins / chemistry, pharmacology* Mannose-Binding Lectin / chemistry, pharmacology* Mice Mice, Inbred C57BL Neuraminidase / antagonists & inhibitors Recombinant Fusion Proteins / chemistry, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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R21 AI077081-01/AI/NIAID NIH HHS; R21 AI077081-01A1/AI/NIAID NIH HHS; U01 AI070330/AI/NIAID NIH HHS; U01 AI070330-01/AI/NIAID NIH HHS; U01 AI074503-01/AI/NIAID NIH HHS; U01 AI074503-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antiviral Agents; 0/Lectins; 0/Mannose-Binding Lectin; 0/Recombinant Fusion Proteins; 0/ficolin; EC 3.2.1.18/Neuraminidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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