Targeting UBE4A Revives Viperin Protein in Epithelium to Enhance Host Antiviral Defense

作者: Yukang Yuan , Ying Miao , Liping Qian , Yang Zhang , Chao Liu

DOI: 10.1016/J.MOLCEL.2019.11.003

关键词: Protein biosynthesisUbiquitinAcetyltransferaseInterferonProtein degradationHAT1ViperinBiologyAntiviral proteinCell biology

摘要: Mutation and prevalence of pathogenic viruses prompt the development broad-spectrum antiviral strategies. Viperin is a potent protein that inhibits broad range viruses. Unexpectedly, we found production in epithelium defective response to both interferons (IFNs). We further revealed IFNs stimulate expression acetyltransferase HAT1, which induces Lys197-acetylation on Viperin. acetylation turn recruits UBE4A stimulates K6-linked polyubiquitination at Lys206 Viperin, leading degradation. Importantly, deficiency restores epithelium. then designed interfering peptides (IPs) inhibit binding with VIP-IP3 rescues therefore enhances cellular activity. renders mice more resistant viral infection. These findings could provide strategies for enhancing host improving efficacy IFN-based therapy.

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