Shah, K. M., Stewart, S. E., Wei, W., Woodman, Ciaran B. J., O'Neil, J. D., Dawson, Christopher W. and Young, Lawrence S.. (2009) The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation. Oncogene, Vol.28 (No.44). pp. 3903-3914. ISSN 0950-9232

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Abstract

Although frequently expressed in Epstein–Barr virus (EBV)-positive malignancies, the role that latent membrane protein 2A and 2B (LMP2A and LMP2B) have in the oncogenic process remains obscure. Here we show a novel function for these proteins in epithelial cells, namely, their ability to modulate signalling from type I/II interferon receptors (IFNRs). We show that LMP2A- and LMP2B-expressing epithelial cells show decreased responsiveness to interferon (IFN)α and IFNγ, as assessed by STAT1 phosphorylation, ISGF3 and GAF-mediated binding to IFN-stimulated response element and IFNγ-activated factor sequence elements and luciferase reporter activation. Transcriptional profiling highlighted the extent of this modulation, with both viral proteins impacting ‘globally’ on IFN-stimulated gene expression. Although not affecting the levels of cell-surface IFNRs, LMP2A and LMP2B accelerated the turnover of IFNRs through processes requiring endosome acidification. This function may form part of EBV's strategy to limit anti-viral responses and define a novel function for LMP2A and LMP2B in modulating signalling from receptors that participate in innate immune responses.

Item Type:	Journal Article
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Oncogene
Publisher:	Nature Publishing Group
ISSN:	0950-9232
Official Date:	5 November 2009
Volume:	Vol.28
Number:	No.44
Page Range:	pp. 3903-3914
Identification Number:	10.1038/onc.2009.249
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/51863

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