GRP75 blocks hepatitis E virus infection by targeting HEV-ORF2 for degradation through chaperone-mediated autophagy and promoting IRF3 activation
Due to the lack of an effective <i>in vitro</i> model, the viral-host interaction of HEV remains largely elusive. This study uncovers a novel mechanism by which GRP75 inhibits HEV infection. On one hand, the GRP75 protein facilitates the degradation of HEV-ORF2 through the lysosome-associated, chaperone-mediated autophagy by recognizing KFERQ-like motif presented on HEV-ORF2. On the other hand, GRP75 enhances the production of IFN-β by promoting interaction between MAVS and TBK1, thereby establishing an antiviral state and suppressing HEV infection. This research expands our current understanding of host resistance to HEV and provides a new function of GRP75, suggesting that GRP75 might be a novel antiviral factor against virus infection.
Authors
- Zhijie An (ORCID: https://orcid.org/0000-0002-1552-6684)
- Chunyan Wu (ORCID: https://orcid.org/0000-0003-3192-3126)
- Rong Xu (ORCID: https://orcid.org/0000-0003-3876-6573)
- Qin Zhao (ORCID: https://orcid.org/0000-0002-8993-7494)
- Chao Xu (ORCID: https://orcid.org/0000-0003-0444-7080)
- Yuchen Nan (ORCID: https://orcid.org/0000-0002-4442-8004)
- Tong Yuan (ORCID: https://orcid.org/0000-0003-3211-1322)
- Yajing Wang (ORCID: https://orcid.org/0009-0002-3353-8547)
- Yafei Li (ORCID: https://orcid.org/0000-0003-1158-7671)
- Xin Yin (ORCID: https://orcid.org/0000-0003-2357-6718)
- Yonglin Yang (ORCID: https://orcid.org/0000-0003-3162-4070)
- Cuiyu Ba
- Zhaobin Zhou
Institutions
- Nantong University (CN)
- The Affiliated Taizhou People's Hospital of Nanjing Medical University (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Harbin Veterinary Research Institute (CN)
- Jiangxi Agricultural University (CN)
- Nanjing Medical University (CN)
- Northwest A&F University (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1128/jvi.01344-25
- Primary Topic
- Toxoplasma gondii Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00