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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\u2010regulated autophagy involves in HTNV replication is unknown. Here, we identified that HTNV infection inhibits PTEN expression in\u00a0vitro and in\u00a0vivo. The HTNV glycoprotein Gc promotes PTEN ubiquitination and degradation through 26S\u2010proteasome 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.<\/jats:p>","DOI":"10.1096\/fj.202401916r","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T10:44:51Z","timestamp":1736505891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hantaan virus glycoprotein Gc induces NEDD4\u2010dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation"],"prefix":"10.1096","volume":"39","author":[{"given":"Shuang","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, Institute of Medical Virology, Taikang Medical School (School of Basic Medical Sciences) Wuhan University  Wuhan Hubei China"},{"name":"College of Life Sciences South\u2010Central Minzu University  Wuhan Hubei 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