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Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis that is closely associated with several human malignant diseases, while type I interferon (IFN-I) plays an important role against EBV infection. As we all know, EBV can encode some proteins to inhibit the production of IFN-I...

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Autores principales: Wang, Ping, Deng, Yangxi, Guo, Yingjie, Xu, Zuo, Li, Yiwen, Ou, Xiaowen, Xie, Li, Lu, Manjiao, Zhong, Jiayi, Li, Bolin, Hu, Li, Deng, Shenyu, Peng, Tao, Cai, Mingsheng, Li, Meili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774019/
https://www.ncbi.nlm.nih.gov/pubmed/33391252
http://dx.doi.org/10.3389/fimmu.2020.513383
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author Wang, Ping
Deng, Yangxi
Guo, Yingjie
Xu, Zuo
Li, Yiwen
Ou, Xiaowen
Xie, Li
Lu, Manjiao
Zhong, Jiayi
Li, Bolin
Hu, Li
Deng, Shenyu
Peng, Tao
Cai, Mingsheng
Li, Meili
author_facet Wang, Ping
Deng, Yangxi
Guo, Yingjie
Xu, Zuo
Li, Yiwen
Ou, Xiaowen
Xie, Li
Lu, Manjiao
Zhong, Jiayi
Li, Bolin
Hu, Li
Deng, Shenyu
Peng, Tao
Cai, Mingsheng
Li, Meili
author_sort Wang, Ping
collection PubMed
description Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis that is closely associated with several human malignant diseases, while type I interferon (IFN-I) plays an important role against EBV infection. As we all know, EBV can encode some proteins to inhibit the production of IFN-I, but it’s not clear whether other proteins also take part in this progress. EBV early lytic protein BFRF1 is shown to be involved in viral maturation, however, whether BFRF1 participates in the host innate immune response is still not well known. In this study, we found BFRF1 could down-regulate sendai virus-induced IFN-β promoter activity and mRNA expression of IFN-β and ISG54 during BFRF1 plasmid transfection and EBV lytic infection, but BFRF1 could not affect the promoter activity of NF-κB or IRF7. Specifically, BFRF1 could co-localize and interact with IKKi. Although BFRF1 did not interfere the interaction between IKKi and IRF3, it could block the kinase activity of IKKi, which finally inhibited the phosphorylation, dimerization, and nuclear translocation of IRF3. Taken together, BFRF1 may play a critical role in disrupting the host innate immunity by suppressing IFN-β activity during EBV lytic cycle.
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spelling pubmed-77740192021-01-01 Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3 Wang, Ping Deng, Yangxi Guo, Yingjie Xu, Zuo Li, Yiwen Ou, Xiaowen Xie, Li Lu, Manjiao Zhong, Jiayi Li, Bolin Hu, Li Deng, Shenyu Peng, Tao Cai, Mingsheng Li, Meili Front Immunol Immunology Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis that is closely associated with several human malignant diseases, while type I interferon (IFN-I) plays an important role against EBV infection. As we all know, EBV can encode some proteins to inhibit the production of IFN-I, but it’s not clear whether other proteins also take part in this progress. EBV early lytic protein BFRF1 is shown to be involved in viral maturation, however, whether BFRF1 participates in the host innate immune response is still not well known. In this study, we found BFRF1 could down-regulate sendai virus-induced IFN-β promoter activity and mRNA expression of IFN-β and ISG54 during BFRF1 plasmid transfection and EBV lytic infection, but BFRF1 could not affect the promoter activity of NF-κB or IRF7. Specifically, BFRF1 could co-localize and interact with IKKi. Although BFRF1 did not interfere the interaction between IKKi and IRF3, it could block the kinase activity of IKKi, which finally inhibited the phosphorylation, dimerization, and nuclear translocation of IRF3. Taken together, BFRF1 may play a critical role in disrupting the host innate immunity by suppressing IFN-β activity during EBV lytic cycle. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7774019/ /pubmed/33391252 http://dx.doi.org/10.3389/fimmu.2020.513383 Text en Copyright © 2020 Wang, Deng, Guo, Xu, Li, Ou, Xie, Lu, Zhong, Li, Hu, Deng, Peng, Cai and Li http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Ping
Deng, Yangxi
Guo, Yingjie
Xu, Zuo
Li, Yiwen
Ou, Xiaowen
Xie, Li
Lu, Manjiao
Zhong, Jiayi
Li, Bolin
Hu, Li
Deng, Shenyu
Peng, Tao
Cai, Mingsheng
Li, Meili
Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title_full Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title_fullStr Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title_full_unstemmed Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title_short Epstein-Barr Virus Early Protein BFRF1 Suppresses IFN-β Activity by Inhibiting the Activation of IRF3
title_sort epstein-barr virus early protein bfrf1 suppresses ifn-β activity by inhibiting the activation of irf3
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774019/
https://www.ncbi.nlm.nih.gov/pubmed/33391252
http://dx.doi.org/10.3389/fimmu.2020.513383
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