NPC1 promotes HTNV replication by controlling innate immune response.

Hantaan virus (HTNV) causes the majority of hemorrhagic fever with renal syndrome (HFRS) across Asia, which imposes a substantial public health burden. Virus-host interaction, particularly protein-protein interactions, essentially determined the clinic outcomes of HFRS patients; however, the interactions between HTNV and host proteins remain largely uncharacterized. 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.