Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Binds to p65/ Rel A and p50/NF-κB1 To Inhibits TNF-α-induced NF-κB Activity

作者:Jie Zhang;Shuai Wang;Kezhen Wang;Chunfu Zheng 刊名: 上传者:罗俊

【摘要】Nuclear factor κB(NF-κB) plays central roles in the regulation of diverse biological processes, including innate and adaptive immunity, inflammation, cell proliferation, activation and cell survival.Herpes simplex virus 1(HSV-1) is the archetypal member of the alphaherpesvirus with a large genome encoding over 80 viral proteins, many of which are involved in virus-host interactions and show immune modulatory capabilities.In this study, we demonstrated that the HSV-1 ICP0 protein, a viral E3 ubiquitin ligase, was an antagonism of the canonical NF-κB signaling pathway.ICP0 was shown to significantly suppress tumor necrosis factor-α(TNF-α) mediated NF-κB activation.Co-immunoprecipitation experiments revealed that ICP0 bind to the NF-κB subunit p65 and p50.As observed by fluorescence microscopy, ICP0 abolished nuclear translocation of p65 upon TNF-α stimulated; and we also found that ICP0 degraded p50 by its E3 ubiquitin ligase activity.The Ring finger domain mutant ICP0 did not inhibit TNF-α mediated NF-κB activation, p65 nuclear translocation and p50 degradation.Taken together, the data indicated that HSV-1 ICP0 interacted with p65 and p50, degraded p50 through the ubiquitin-proteasome pathway and prevented NF-κB dependent gene expression, which maycontribute to immune evasion of HSV-1.

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