2. Academic Validation
  3. CDC42 supports HBV entry by NTCP translocation to the plasma membrane and macropinocytosis

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

  • EMBO Rep. 2025 Sep 15. doi: 10.1038/s44319-025-00581-8.
Shuzhi Cui # 1 2,  Wei Gao # 2 3 4,  Yuxin Chen # 5,  Yi Xu 1,  Zhifang Li 2,  Yu Wei 6 7,  Yaming Jiu 8 9 10
Affiliations

Affiliations

  • 1 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.
  • 2 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.
  • 4 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China.
  • 5 Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, China.
  • 6 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China. yu.wei@pasteur.fr.
  • 7 Institut Pasteur, Université Paris Cité, 28 rue du Dr. Roux, Paris, 75015, France. yu.wei@pasteur.fr.
  • 8 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, 200031, Shanghai, China. ymjiu@siii.cas.cn.
  • 9 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China. ymjiu@siii.cas.cn.
  • 10 University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, 100049, Beijing, China. ymjiu@siii.cas.cn.
  • # Contributed equally.
PMID: 40954218 DOI: 10.1038/s44319-025-00581-8
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.

Keywords

CDC42; Hepatitis B Virus; Macropinocytosis; Sodium Taurocholate Cotransporting Polypeptide; Virus Entry.

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