Abstract:
:Mutation and prevalence of pathogenic viruses prompt the development of broad-spectrum antiviral strategies. Viperin is a potent antiviral protein that inhibits a broad range of viruses. Unexpectedly, we found that Viperin protein production in epithelium is defective in response to both viruses and interferons (IFNs). We further revealed that viruses and IFNs stimulate expression of the acetyltransferase HAT1, which induces Lys197-acetylation on Viperin. Viperin acetylation in turn recruits UBE4A that stimulates K6-linked polyubiquitination at Lys206 of Viperin, leading to Viperin protein degradation. Importantly, UBE4A deficiency restores Viperin protein production in epithelium. We then designed interfering peptides (IPs) to inhibit UBE4A binding with Viperin. We found that VIP-IP3 rescues Viperin protein production in epithelium and therefore enhances cellular antiviral activity. VIP-IP3 renders mice more resistant to viral infection. These findings could provide strategies for both enhancing host broad-spectrum antiviral response and improving the efficacy of IFN-based antiviral therapy.
journal_name
Mol Celljournal_title
Molecular cellauthors
Yuan Y,Miao Y,Qian L,Zhang Y,Liu C,Liu J,Zuo Y,Feng Q,Guo T,Zhang L,Chen X,Jin L,Huang F,Zhang H,Zhang W,Li W,Xu G,Zheng Hdoi
10.1016/j.molcel.2019.11.003subject
Has Abstractpub_date
2020-02-20 00:00:00pages
734-747.e7issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(19)30832-9journal_volume
77pub_type
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