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The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation
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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. doi:10.1038/onc.2009.249
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Official URL: http://dx.doi.org/10.1038/onc.2009.249
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 Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
| Journal or Publication Title: | Oncogene | ||||
| Publisher: | Nature Publishing Group | ||||
| ISSN: | 0950-9232 | ||||
| Official Date: | 5 November 2009 | ||||
| Dates: |
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| Volume: | Vol.28 | ||||
| Number: | No.44 | ||||
| Page Range: | pp. 3903-3914 | ||||
| DOI: | 10.1038/onc.2009.249 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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