Scavenger Receptor class F member 2 is an intracellular receptor for Hepatitis B virus

Li, C.; Wang, Y.; Xiong, R.; Li, Q.; Zhou, Z.; Liu, Q.; Qi, Y.; Gao, Z.; Xu, G.; Fang, L.; Sun, Y.; Farzan, M.; Choe, H.; Sui, J.; Li, W.

doi:10.1101/2025.06.13.659407

bioRxiv · 10.1101/2025.06.13.659407

Scavenger Receptor class F member 2 is an intracellular receptor for Hepatitis B virus

Li, C.·Wang, Y.·Xiong, R.·Li, Q.·Zhou, Z.·Liu, Q.·Qi, Y.·Gao, Z.·Xu, G.·Fang, L.·Sun, Y.·Farzan, M.·Choe, H.·Sui, J.·Li, W.

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Abstract

Hepatitis B virus (HBV) infects hepatocytes by specific binding to the cell-surface receptor --sodium taurocholate cotransporting polypeptide (NTCP)--through the preS1 region of its large envelop protein, followed by a less well understood transport process across the cytoplasm to the nucleus. Here, we report that scavenger receptor class F member 2 (SCARF2), a single-pass transmembrane protein, functions as an intracellular receptor for HBV. SCARF2 binds to a preS1 region downstream of the NTCP binding site through its N-terminal EGF-like domains 4-6, and its proline-rich C-terminal domain also plays an indispensable role in the infection. The internalized HBV virions are transported to the cytoplasmic side of nuclear pore complexes (NPCs) within the SCARF2-containing endosomes. HBV capsid release from the endosomal vesicles is significantly impaired by knockdown of SCARF2. These results suggest a model that SCARF2 conveys HBV to the periphery of NPCs and ultimately leads to viral capsid release for nuclear entry.

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Li, C., Wang, Y., Xiong, R., Li, Q., Zhou, Z., Liu, Q., Qi, Y., Gao, Z., Xu, G., Fang, L., Sun, Y., Farzan, M., Choe, H., Sui, J., Li, W.. 2025-06-13. Scavenger Receptor class F member 2 is an intracellular receptor for Hepatitis B virus. https://doi.org/10.1101/2025.06.13.659407

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