Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus

作者：Haibo Yu, Jihua Ren, Haijun Deng, Linfeng Li, Zhenzhen Zhang, Shengtao Cheng, Zufeng Guo, Ailong Huang, Yongjun Dang, Kunling Song, Daiqing Wu, Xinyan Yao, Yiping Qin, Zhen Yang, Kexin Xu, Xin He, Juan Chen · 发表于：Journal of Hepatology · 年份：2024 · DOI：10.1016/j.jhep.2024.06.032 · 被引用次数：22 · 研究领域：Angiogenesis and VEGF in Cancer、Complement system in diseases、Lipid metabolism and disorders

BACKGROUND & AIMS: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS: Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS: Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs (large hepatitis B surface proteins) and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vi...