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Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease

Lichao Zang1,2, Xinyu Yang1, Yan Chen1

  • 1Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University , Changzhou, Jiangsu, China.

Journal of Virology
|October 5, 2023
PubMed
Abstract

Insights

The host E3 ubiquitin ligase SPOP targets the enterovirus 71 (EV71) nonstructural protein 2Apro for ubiquitination and degradation, revealing a novel antiviral mechanism against EV71 infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Enterovirus 71 (EV71) is a significant pathogen causing severe illness in young children.
  • EV71 infection and replication are modulated by ubiquitination, a key post-translational modification.
  • EV71 evades host immunity by interfering with interferon signaling, but host antiviral ubiquitination mechanisms are largely unknown.

Purpose of the Study:

  • To elucidate the host-mediated ubiquitination mechanisms that restrict EV71 infection.
  • To identify host factors involved in the ubiquitination and degradation of EV71 proteins.

Main Methods:

  • Investigated the ubiquitination status of EV71 nonstructural protein 2Apro.
  • Utilized co-immunoprecipitation and Western blotting to identify interacting host proteins.
  • Assessed the role of SPOP in EV71 protein degradation and viral replication.

Main Results:

  • The EV71 nonstructural protein 2Apro undergoes ubiquitination.
  • The host E3 ubiquitin ligase SPOP directly interacts with and mediates the ubiquitination and subsequent degradation of EV71 2Apro.
  • SPOP plays a crucial role in restricting EV71 infection, representing a novel host antiviral defense.

Conclusions:

  • The host E3 ubiquitin ligase SPOP targets EV71 2Apro for degradation via ubiquitination.
  • This study reveals a previously unrecognized role for SPOP in antiviral immunity against EV71.
  • Targeting SPOP-mediated degradation of EV71 proteins may offer new therapeutic strategies.
Keywords:
2A proteaseEV71SPOPubiquitination

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