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To identify host factors interacting with the HTNV glycoprotein (GP), we combined deep-learning-based virtual screening via MaSIF with immunoprecipitation coupled to mass spectrometry (IP-MS) and found that host cholesterol transporter protein Niemann-Pick C1 (NPC1) binds to HTNV GP and promotes HTNV replication. Specifically, NPC1 mitigates anti-viral innate immune response following HTNV infection, a function not previously documented among its known roles in viral infection. Our findings not only expand current understandings of NPC1 involving viral infection but also highlight its potential as an anti-viral target.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1811629","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:37:59Z","timestamp":1780637879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NPC1 promotes HTNV replication by controlling innate immune response"],"prefix":"10.3389","volume":"17","author":[{"given":"Hansong","family":"Qi","sequence":"first","affiliation":[{"name":"Key Laboratory of Genetic Evolution and Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences","place":["Kunming, 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