CDC42 supports HBV entry by NTCP translocation to the plasma membrane and macropinocytosis.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-09-15 DOI:10.1038/s44319-025-00581-8

Shuzhi Cui, Wei Gao, Yuxin Chen, Yi Xu, Zhifang Li, Yu Wei, Yaming Jiu

引用次数: 0

Abstract

CDC42 is a member of Rho GTPase family that regulates various biological processes and its activity can be hijacked by invading pathogens. Here, we discovered that the level of active CDC42 in hepatocytes positively correlates with the entry capacity of hepatitis B virus (HBV). Mechanistically, CDC42 activation effectively promotes the transport of the viral receptor sodium taurocholate co-transporting polypeptide (NTCP) to the plasma membrane via Rab11 dependent recycling endosomal pathway. NTCP interacts with Rab11 and activation of CDC42 signaling reinforces the interaction between NTCP and Rab11. We further show that clathrin mediated endocytosis (CME), the known HBV entry pathway, is independent of CDC42 activity. Intriguingly, we reveal that CDC42 dependent macropinocytosis is a route for HBV entry, which is equally essential for viral infection as CME. Together, our findings uncover new mechanisms for HBV entry that involve unrecognized functions of CDC42 and suggest that Rho GTPase signaling might represent a potential target for antiviral therapy.

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CDC42通过NTCP易位到质膜和巨噬细胞作用支持HBV进入。

CDC42是调控多种生物过程的Rho GTPase家族成员，其活性可被入侵的病原体劫持。在这里，我们发现肝细胞中活性CDC42的水平与乙型肝炎病毒（HBV）的进入能力呈正相关。在机制上，CDC42激活有效地促进了病毒受体牛磺酸胆酸钠共转运多肽（NTCP）通过Rab11依赖的循环内体途径转运到质膜。NTCP与Rab11相互作用，CDC42信号的激活加强了NTCP与Rab11之间的相互作用。我们进一步表明，网格蛋白介导的内吞作用（CME）是已知的HBV进入途径，与CDC42活性无关。有趣的是，我们发现CDC42依赖性巨噬细胞增多是HBV进入的途径，这对病毒感染和CME同样重要。总之，我们的发现揭示了涉及CDC42未被识别的功能的HBV进入的新机制，并提示Rho GTPase信号可能代表抗病毒治疗的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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