Netrin-1 inhibits the attachment and internalization of Hepatitis B virus for hepatocyte infection.

ABSTRACT: Netrin-1, a secreted laminin-related protein, is increasingly recognized for its role in viral pathogenesis, alongside its established functions in neural guidance and immune regulation. We previously identified endothelial lipase (LIPG) as a host factor that facilitates hepatitis B virus (HBV) attachment via heparan sulfate proteoglycans (HSPGs) and/or the sodium taurocholate cotransporting polypeptide (NTCP). Through LIPG-based screening, we identified Netrin-1 as an LIPG-interacting protein, and synthetic peptides derived from Netrin-1 sequences exhibited potent anti-HBV activity. In primary human hepatocytes, Netrin-1 demonstrated antiviral activity against HBV, and in HepG2-NTCP-YFP cells, it inhibited viral attachment and internalization. Mechanistically, Netrin-1 binds to LIPG throu

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12711026 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature