Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency
Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I...
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ndltd-ETSU-oai-dc.etsu.edu-etsu-works-77842020-07-15T07:09:31Z Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency Ning, Shunbin Wang, Ling Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet the underlying mechanism of this paradoxical phenomenon remains unclear. It is well known that tyrosine phosphorylation of most components of the IFN-I Jak-STAT pathway is essential for its signaling transduction. Thus, we have performed phosphotyrosine proteomics. We have found that the IFN-I Jak-STAT pathway is inactive due to the attenuated STAT2 activity, whereas the IFN-II Jak-STAT pathway is constitutively active, in EBV latency. We further confirmed these results by immunoblotting. This pilot study provides valuable information for the critical question regarding how the IRF7-mediated IFN-I response is evaded by EBV in its latency, and will prompt us to elucidate the underlying mechanisms. 2016-08-05T07:00:00Z text application/pdf https://dc.etsu.edu/etsu-works/6533 https://dc.etsu.edu/cgi/viewcontent.cgi?article=7784&context=etsu-works http://creativecommons.org/licenses/by/4.0/ ETSU Faculty Works Digital Commons @ East Tennessee State University Type I IFN Jak-STAT Pathway EBV Latency Internal Medicine Internal Medicine |
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Type I IFN Jak-STAT Pathway EBV Latency Internal Medicine Internal Medicine Ning, Shunbin Wang, Ling Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
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Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet the underlying mechanism of this paradoxical phenomenon remains unclear. It is well known that tyrosine phosphorylation of most components of the IFN-I Jak-STAT pathway is essential for its signaling transduction. Thus, we have performed phosphotyrosine proteomics. We have found that the IFN-I Jak-STAT pathway is inactive due to the attenuated STAT2 activity, whereas the IFN-II Jak-STAT pathway is constitutively active, in EBV latency. We further confirmed these results by immunoblotting. This pilot study provides valuable information for the critical question regarding how the IRF7-mediated IFN-I response is evaded by EBV in its latency, and will prompt us to elucidate the underlying mechanisms. |
author |
Ning, Shunbin Wang, Ling |
author_facet |
Ning, Shunbin Wang, Ling |
author_sort |
Ning, Shunbin |
title |
Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
title_short |
Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
title_full |
Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
title_fullStr |
Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
title_full_unstemmed |
Inactivation Of Type I IFN Jak-STAT Pathway In EBV Latency |
title_sort |
inactivation of type i ifn jak-stat pathway in ebv latency |
publisher |
Digital Commons @ East Tennessee State University |
publishDate |
2016 |
url |
https://dc.etsu.edu/etsu-works/6533 https://dc.etsu.edu/cgi/viewcontent.cgi?article=7784&context=etsu-works |
work_keys_str_mv |
AT ningshunbin inactivationoftypeiifnjakstatpathwayinebvlatency AT wangling inactivationoftypeiifnjakstatpathwayinebvlatency |
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1719325942913957888 |