2. Academic Validation
  3. ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction

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

  • iScience. 2024 Aug 20;27(9):110757. doi: 10.1016/j.isci.2024.110757.
Shengze Zhang 1 2,  Chuming Luo 1 2,  Qiqi Chen 1 2,  Nina Li 1 2,  Xinzhong Liao 1 2,  Jiani Wu 1 2,  Haolu Zha 1 2,  Ting Xie 1 2,  Shaohui Bai 1 2,  Weijian Tian 1 2,  Lin Zhu 1 2,  Xuan Zou 3,  Shisong Fang 3,  Caijun Sun 1 2 4,  Ying Jiang 5,  Jianhui Yuan 5,  Yuelong Shu 1 4 6,  Nan Wu 5,  Huanle Luo 1 2 4
Affiliations

Affiliations

  • 1 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, P.R. China.
  • 2 School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 510275, P.R. China.
  • 3 Shenzhen Center for Disease Control and Prevention, Shenzhen 518073, P.R. China.
  • 4 Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, P.R. China.
  • 5 Shenzhen Nanshan Center for Disease Control and Prevention, Shenzhen 518054, P.R. China.
  • 6 Key Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102629, P.R. China.
PMID: 39280623 DOI: 10.1016/j.isci.2024.110757
Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial in Flavivirus infections, modulating the host immune response through interactions with Viral Proteins. Despite its importance, the relationship between TRAF6 and Zika virus (ZIKV) remains poorly understood. Our prior proteomics analysis revealed reduced TRAF6 protein levels in ZIKV-infected human trophoblast cells compared to non-infected controls. Subsequent studies in cell models and murine tissues confirmed a significant reduction in both TRAF6 mRNA and protein levels post-ZIKV Infection. Further investigations unveiled that ZIKV induces P62-mediated degradation of TRAF6, with NS1 identified as the primary contributor. Co-localization and interaction studies demonstrated that NS1 promotes the association of p62, a key Autophagy mediator, with TRAF6. Notably, our findings revealed TRAF6 enhances ZIKV Infection, NS1 ubiquitination, NS1 expression, and the production of inflammatory cytokines and chemokines. These insights highlight the intricate TRAF6-ZIKV relationship, offering potential for drug targeting NS1-TRAF6 interactions to manage ZIKV infections effectively.

Keywords

Biological sciences; Molecular biology; Natural sciences; Virology.

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