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Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells

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Title: Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells
Authors: Giotis, ES
Ross, CS
Robey, RC
Nohturfft, A
Goodbourn, S
Skinner, MA
Item Type: Journal Article
Abstract: The spontaneously immortalised DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEFs) for studies on avian viruses such as avian influenza but no comprehensive study has as yet been reported comparing their innate immunity phenotypes. We conducted microarray analyses of DF-1 and CEFs, under both normal and stimulated conditions using chicken interferon-α (chIFNα) and the attenuated infectious bursal disease virus vaccine strain PBG98. We found that DF-1 have an attenuated innate response compared to CEFs. Basal expression levels of Suppressor of Cytokine Signalling 1 (chSOCS1), a negative regulator of cytokine signalling in mammals, are 16-fold higher in DF-1 than in CEFs. The chSOCS1 “SOCS box” domain (which, in mammals, interacts with an E3 ubiquitin ligase complex) is not essential for the inhibition of cytokine-induced JAK/STAT signalling activation in DF-1. Overexpression of SOCS1 in chIFNα-stimulated DF-1 led to a relative decrease in expression of interferon-stimulated genes (ISGs; MX1 and IFIT5) and increased viral yield in response to PBG98 infection. Conversely, knockdown of SOCS1 enhanced induction of ISGs and reduced viral yield in chIFNα-stimulated DF-1. Consequently, SOCS1 reduces induction of the IFN signalling pathway in chicken cells and can potentiate virus replication.
Issue Date: 13-Dec-2017
Date of Acceptance: 29-Nov-2017
URI: http://hdl.handle.net/10044/1/54412
DOI: https://dx.doi.org/10.1038/s41598-017-17730-2
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/H005323/1
Publication Status: Published
Article Number: 17485
Appears in Collections:Department of Medicine (up to 2019)