ISG12a restricts hepatitis C virus infection through the ubiquitination-dependent degradation pathway

Binbin Xue, Darong Yang, Jingjing Wang, Yan Xu, Xiaohong Wang, Yuwen Qin, Renyun Tian, Shengwen Chen, Qinya Xie, Nianli Liu, Haizhen Zhua

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Interferons (IFNs) restrict various kinds of viral infection via induction of hundreds of IFN-stimulated genes (ISGs), while the functions of the majority of ISGs are broadly unclear. Here, we show that a high-IFN-inducible gene, ISG12a (also known as IFI27), exhibits a nonapoptotic antiviral effect on hepatitis C virus (HCV) infection. Viral NS5A protein is targeted specifically by ISG12a, which mediates NS5A degradation via a ubiquitination-dependent proteasomal pathway. K374R mutation in NS5A domain III abrogates ISG12a-induced ubiquitination and degradation of NS5A. S-phase kinase-associated protein 2 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. ISG12a functions as a crucial adaptor that promotes SKP2 to interact with and degrade viral protein. Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity of SKP2. These findings uncover an intriguing mechanism by which ISG12a restricts viral infection and provide clues for understanding the actions of innate immunity.

Original languageEnglish (US)
Pages (from-to)6832-6845
Number of pages14
JournalJournal of Virology
Volume90
Issue number15
DOIs
StatePublished - Jan 1 2016

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S-Phase Kinase-Associated Proteins
Hepatitis C virus
Ubiquitination
Virus Diseases
interferons
Hepacivirus
interphase
Interferons
phosphotransferases (kinases)
Ubiquitin-Protein Ligases
viral proteins
Viral Proteins
Antiviral Agents
degradation
infection
Genes
ubiquitin-protein ligase
genes
proteins
ligases

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

ISG12a restricts hepatitis C virus infection through the ubiquitination-dependent degradation pathway. / Xue, Binbin; Yang, Darong; Wang, Jingjing; Xu, Yan; Wang, Xiaohong; Qin, Yuwen; Tian, Renyun; Chen, Shengwen; Xie, Qinya; Liu, Nianli; Zhua, Haizhen.

In: Journal of Virology, Vol. 90, No. 15, 01.01.2016, p. 6832-6845.

Research output: Contribution to journalArticle

Xue, B, Yang, D, Wang, J, Xu, Y, Wang, X, Qin, Y, Tian, R, Chen, S, Xie, Q, Liu, N & Zhua, H 2016, 'ISG12a restricts hepatitis C virus infection through the ubiquitination-dependent degradation pathway', Journal of Virology, vol. 90, no. 15, pp. 6832-6845. https://doi.org/10.1128/JVI.00352-16
Xue, Binbin ; Yang, Darong ; Wang, Jingjing ; Xu, Yan ; Wang, Xiaohong ; Qin, Yuwen ; Tian, Renyun ; Chen, Shengwen ; Xie, Qinya ; Liu, Nianli ; Zhua, Haizhen. / ISG12a restricts hepatitis C virus infection through the ubiquitination-dependent degradation pathway. In: Journal of Virology. 2016 ; Vol. 90, No. 15. pp. 6832-6845.
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