Hepadnavirus tropism determined by diversified NTCP functionality in Feline species

Lion feline NTCP shows markedly reduced bile acid transport and lacks preS1 binding, while cat, tiger, and leopard NTCPs support hepadnavirus entry and infection.

• Why it matters: HBV’s narrow host range is linked to NTCP, but feline NTCPs show unexpected functional diversity that could explain species-specific susceptibility and receptor evolution.
• What they did: The study profiled NTCP homologs from 23 mammalian species, tested preS1 binding and HBV infection, performed productive infection in primary cat hepatocytes, and used mutagenesis at positions 191 and 268.
• The result: Double substitutions (G191R and T268A) in cat-NTCP abolished preS1 binding, while reciprocal changes restored lion-NTCP receptor function; this also matched susceptibility differences to feline-infected domestic cat HBV.

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