التفاصيل البيبلوغرافية
| العنوان: |
Epstein-Barr virus activates F-box protein FBXO2 to limit viral infectivity by targeting glycoprotein B for degradation. |
| المؤلفون: |
Zhang, Hao-Jiong, Tian, Jinxiu, Qi, Xue-Kang, Xiang, Tong, He, Gui-Ping, Zhang, Hua, Yu, Xibao, Zhang, Xiao, Zhao, Bingchun, Feng, Qi-Sheng, Chen, Ming-Yuan, Zeng, Mu-Sheng, Zeng, Yi-Xin, Feng, Lin |
| المصدر: |
PLoS Pathogens; 7/27/2018, Vol. 14 Issue 7, p1-22, 22p |
| مصطلحات موضوعية: |
EPSTEIN-Barr virus, ENDOPLASMIC reticulum, GLYCOSYLATION, GLYCOMICS, UBIQUITIN, PATHOGENIC microorganisms |
| مستخلص: |
Epstein-Barr virus (EBV) is a human cancer-related virus closely associated with lymphoid and epithelial malignancies, and EBV glycoprotein B (gB) plays an essential role in viral entry into both B cells and epithelial cells by promoting cell-cell fusion. EBV gB is exclusively modified with high-mannose-linked N-glycans and primarily localizes to the endoplasmic reticulum (ER) with low levels on the plasma membrane (PM). However, the mechanism through which gB is regulated within host cells is largely unknown. Here, we report the identification of F-box only protein 2 (FBXO2), an SCF ubiquitin ligase substrate adaptor that preferentially binds high-mannose glycans and attenuates EBV infectivity by targeting N-glycosylated gB for degradation. gB possesses seven N-glycosylation sites, and FBXO2 directly binds to these high-mannose moieties through its sugar-binding domain. The interaction promotes the degradation of glycosylated gB via the ubiquitin-proteasome pathway. Depletion of FBXO2 not only stabilizes gB but also promotes its transport from the ER to the PM, resulting in enhanced membrane fusion and viral entry. FBXO2 is expressed in epithelial cells but not B cells, and EBV infection up-regulates FBXO2 levels. In summary, our findings highlight the significance of high-mannose modification of gB and reveal a novel host defense mechanism involving glycoprotein homeostasis regulation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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