English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/133355
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Comparative biochemical and functional analysis of viral and human secreted tumor necrosis factor (TNF) decoy receptors

AuthorsPontejo, Sergio M.; Alejo, Alí; Alcamí, Antonio
Issue Date26-Jun-2015
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 290: 15973- 15984 (2015)
Abstract© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs.
URIhttp://hdl.handle.net/10261/133355
DOI10.1074/jbc.M115.650119
Identifiersdoi: 10.1074/jbc.M115.650119
issn: 1083-351X
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
Alcamí A Comparative Biochemical.pdf1,69 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.