ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction
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.
Authors
- Huanle Luo (ORCID: https://orcid.org/0000-0002-0367-6888)
- Jianhui Yuan (ORCID: https://orcid.org/0000-0001-9200-3871)
- Caijun Sun (ORCID: https://orcid.org/0000-0002-2000-7053)
- Shengze Zhang
- Nina Li
- Qiqi Chen (ORCID: https://orcid.org/0009-0001-8920-2711)
- Shaohui Bai
- Nan Wu (ORCID: https://orcid.org/0000-0002-5638-8134)
- Xuan Zou (ORCID: https://orcid.org/0000-0002-1145-5508)
- Chuming Luo
- Ting Xie (ORCID: https://orcid.org/0000-0001-7471-0943)
- Ying Jiang (ORCID: https://orcid.org/0000-0003-2432-8011)
- Shisong Fang (ORCID: https://orcid.org/0000-0003-1684-5246)
- Jiani Wu (ORCID: https://orcid.org/0000-0003-4954-0692)
- Yuelong Shu (ORCID: https://orcid.org/0000-0001-9279-0916)
- Weijian Tian
- Lin Zhu (ORCID: https://orcid.org/0000-0003-2272-5769)
- Haolu Zha
- Xinzhong Liao
Institutions
- Sun Yat-sen University (CN)
- Shenzhen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Shenzhen Center for Disease Control and Prevention (CN)
- Shenzhen University Health Science Center (CN)
- Shenzhen Nanshan Center for Chronic Disease Control (CN)
Publication Details
- Journal
- iScience
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1016/j.isci.2024.110757
- Citations
- 1
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.54
Funders
- National Natural Science Foundation of China
- Sanming Project of Medicine in Shenzhen
- Science and Technology Planning Project of Guangdong Province