Hantaan virus glycoprotein Gc induces NEDD4‐dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation
Hantaan virus (HTNV) infection causes severe hemorrhagic fever with renal syndrome (HFRS) in humans and the infectious process can be regulated by autophagy. The phosphatase and tensin homolog (PTEN) protein has antiviral effects and plays a critical role in the autophagy pathway. However, the relationship between PTEN and HTNV infection is not clear and whether PTEN-regulated autophagy involves in HTNV replication is unknown. Here, we identified that HTNV infection inhibits PTEN expression in vitro and in vivo. The HTNV glycoprotein Gc promotes PTEN ubiquitination and degradation through 26S-proteasome pathway via the E3 ubiquitin ligase NEDD4. In addition, knockdown of PTEN prevents autophagy and increases HTNV production, while overexpression of PTEN induces autophagosome formation which can wrap HTNV particles, thus leading to restrain the production of progeny viruses. Altogether, our findings reveal the role of PTEN in HTNV infection by autophagy, highlighting the potential importance of PTEN and autophagy in the treatment of HFRS diseases.
Authors
- Y. Jiang
- Shuang Lü (ORCID: https://orcid.org/0000-0001-8700-0254)
- Shuliang Chen (ORCID: https://orcid.org/0000-0002-5240-6665)
- Deyin Guo (ORCID: https://orcid.org/0000-0002-8297-0814)
- Mingyang Li (ORCID: https://orcid.org/0000-0001-9283-4384)
- Tomas Strandin (ORCID: https://orcid.org/0000-0002-2454-7479)
- Xingyuan Chen (ORCID: https://orcid.org/0000-0002-9061-6524)
- Xiaoli Mou
- Hairong Xiong (ORCID: https://orcid.org/0000-0002-4028-0639)
- Yuqing Zhang (ORCID: https://orcid.org/0000-0001-5636-5496)
- Yuanyuan Liu (ORCID: https://orcid.org/0000-0001-6996-7517)
- Yirong Li (ORCID: https://orcid.org/0000-0002-5619-1614)
- Wei Hou (ORCID: https://orcid.org/0000-0003-1439-455X)
- Luo Fan (ORCID: https://orcid.org/0000-0001-9812-2476)
- Liangjun Chen (ORCID: https://orcid.org/0000-0002-9529-9126)
- Shaowei Zhu
- Zhou-Fu Xiang
Institutions
- University of Helsinki (FI)
- Minzu University of China (CN)
- Wuhan University (CN)
- Guangzhou Experimental Station (CN)
- City University of Hong Kong, Shenzhen Research Institute (CN)
- Wuhan Institute of Virology (CN)
- Zhongnan Hospital of Wuhan University (CN)
Publication Details
- Journal
- The FASEB Journal
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1096/fj.202401916r
- Citations
- 2
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hubei Province