近日，日本卫生安全研究所Akihide Ryo及其小组探明了CD46通过顺式相互作用调节细胞表面NTCP水平调控乙型肝炎病毒的进入。相关论文于2025年12月23日发表于国际顶尖学术期刊《分子细胞生物学报》杂志上。

该课题组研究人员发现CD46是NTCP膜表达的关键调控因子。通过基于接近度的标记筛选，课题组发现CD46与NTCP在质膜上顺时针相互作用。CD46的缺失显著降低了肝细胞表面NTCP水平和HBV感染。抗CD46单克隆抗体，特别是克隆E4.3，通过触发NTCP从质膜内化到细胞内囊泡来抑制HBV感染。CD46抗体的抗病毒作用也在人原代肝细胞中得到证实。他们的研究揭示了一种以前未知的调节NTCP介导的HBV进入的机制，并提示CD46是HBV感染的潜在治疗靶点。

研究人员表示，乙型肝炎病毒（HBV）感染仍然是一项重大的全球卫生挑战。虽然牛磺胆酸钠共转运多肽（NTCP）是HBV进入的主要受体，但调控NTCP介导的病毒进入的分子机制仍不完全清楚。

附：英文原文

Title: CD46 regulates hepatitis B virus entry by modulating cell-surface NTCP levels through cis-interaction

Author: Miyakawa, Kei, Nakai, Yusuke, Kameya, Taichi, Nishitsuji, Hironori, Watashi, Koichi, Takeda, Makoto, Seya, Tsukasa, Shimotohno, Kunitada, Kimura, Yayoi, Ryo, Akihide

Issue&Volume: 2025-12-23

Abstract: Hepatitis B virus (HBV) infection remains a major global health challenge. While sodium taurocholate co-transporting polypeptide (NTCP) is the primary receptor for HBV entry, the molecular mechanisms regulating NTCP-mediated viral entry remain incompletely understood. Here, we identified CD46 as a crucial regulatory factor for NTCP membrane expression. We found that CD46 interacted with NTCP in cis at the plasma membrane through proximity-based labeling screening. The depletion of CD46 significantly reduced cell-surface NTCP levels and HBV infection in hepatocytes. Anti-CD46 monoclonal antibodies, particularly clone E4.3, inhibited HBV infection by triggering NTCP internalization from the plasma membrane to intracellular vesicles. The antiviral effect of CD46 antibodies was also confirmed in primary human hepatocytes. Our study reveals a previously unknown mechanism regulating NTCP-mediated HBV entry and suggests CD46 as a potential therapeutic target for HBV infection.

DOI: 10.1093/jmcb/mjaf055

Source: https://academic.oup.com/jmcb/advance-article/doi/10.1093/jmcb/mjaf055/8402925searchresult=1