Glycosylation of
proteins and
lipids in viruses and their host cells is important for
viral infection and is a target for
antiviral therapy. Hepatitis B virus (HBV) is a major pathogen that causes acute and
chronic hepatitis; it cannot be cured because of the persistence of its covalently closed
circular DNA (cccDNA) in hepatocytes. Here we found that Pholiota squarrosa
lectin (PhoSL), a
lectin that specifically binds core
fucose, bound to HBV particles and inhibited HBV
infection of a modified human HepG2 cell line, HepG2-hNTCP-C4, that expresses an HBV receptor,
sodium taurocholate cotransporting polypeptide. Knockout of
fucosyltransferase 8, the
enzyme responsible for core fucosylation and that
aids receptor endocytosis, in HepG2-hNTCP-C4 cells reduced HBV infectivity, and PhoSL facilitated that reduction. PhoSL also blocked the activity of
epidermal growth factor receptor, which usually enhances HBV
infection. HBV particles bound to fluorescently labeled PhoSL internalized into HepG2-hNTCP-C4 cells, suggesting that PhoSL might inhibit HBV
infection after internalization. As PhoSL reduced the formation of HBV cccDNA, a marker of chronic HBV
infection, we suggest that PhoSL could impair processes from internalization to cccDNA formation. Our finding could lead to the development of new anti-HBV agents.