The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
School of Medicine >
Clinical Medicine >
Clinical Medicine (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/63919

Title: Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses.
Author: FALLON, PADRAIC GERARD
Author's Homepage: http://people.tcd.ie/pfallon
Keywords: immunology
inflammation
Herpes
HSV
Chemokines
secreted glycoprotein G
SgG
Issue Date: 2-Feb-2012
Publisher: Public Library of Science
Citation: Viejo-Borbolla A, Martinez-Martín N, Nel HJ, Rueda P, Martín R, Blanco S, Arenzana-Seisdedos F, Thelen M, Fallon PG, Alcamí A., Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses., PLoS Pathogens,2010, Feb;8(2)
Series/Report no.: PLoS Pathogens;8, 2
Abstract: Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell-binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/63919
Appears in Collections:Clinical Medicine (Scholarly Publications)

Files in This Item:

File Description SizeFormat
PLoSPath 2012.pdfPublished (publisher's copy) - Peer Reviewed1.47 MBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback