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Updated: Jun 13, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

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ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction

Shengze Zhang1,2, Chuming Luo1,2, Qiqi Chen1,2

  • 1School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, P.R. China.

Iscience
|September 16, 2024
PubMed

Insights

Zika virus (ZIKV) infection reduces levels of tumor necrosis factor receptor-associated factor 6 (TRAF6) by promoting its degradation. TRAF6 enhances ZIKV infection and inflammatory responses, suggesting targeting NS1-TRAF6 interactions could manage ZIKV.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Tumor necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in flavivirus infections.
  • The specific interaction between TRAF6 and Zika virus (ZIKV) is not well understood.
  • Previous studies indicated reduced TRAF6 levels in ZIKV-infected cells.

Purpose of the Study:

  • To elucidate the relationship between TRAF6 and ZIKV.
  • To investigate the mechanism by which ZIKV affects TRAF6 levels.
  • To determine the role of TRAF6 in ZIKV pathogenesis.

Main Methods:

  • Proteomics analysis to assess TRAF6 protein levels.
  • Quantitative PCR to measure TRAF6 mRNA levels.
  • Co-localization and interaction studies to examine protein associations.
  • Western blotting to detect protein ubiquitination and expression.

Main Results:

  • ZIKV infection significantly reduces both TRAF6 mRNA and protein levels in human cells and murine tissues.
  • ZIKV's NS1 protein induces P62-mediated degradation of TRAF6 via autophagy.
  • TRAF6 was found to enhance ZIKV infection, NS1 ubiquitination and expression, and the production of inflammatory cytokines and chemokines.

Conclusions:

  • ZIKV infection leads to TRAF6 degradation through the NS1-P62-autophagy pathway.
  • TRAF6 positively regulates ZIKV infection and associated inflammatory responses.
  • Targeting the NS1-TRAF6 interaction presents a potential therapeutic strategy for ZIKV infections.
Keywords:
Biological sciencesMolecular biologyNatural sciencesVirology

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