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  3. The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells

The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells

  • BMC Biol. 2024 Jan 25;22(1):12. doi: 10.1186/s12915-024-01819-y.
Huazhang Zhu # 1,  Dawei Wang # 1,  Zuodong Ye # 1,  Lihong Huang 2 3,  Wenjie Wei 4,  Kui Ming Chan 5,  Rongxin Zhang 6,  Liang Zhang 5,  Jianbo Yue 7 8
Affiliations

Affiliations

  • 1 City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
  • 2 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
  • 3 Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
  • 4 Research Core Facilities, Southern University of Science and Technology of China, Shenzhen, 518052, China.
  • 5 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
  • 6 Laboratory of Immunology and Inflammation, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
  • 7 City University of Hong Kong Shenzhen Research Institute, Shenzhen, China. jianbo.yue@duke.edu.
  • 8 Divison of Natural and Applied Sciences, Synear Molecular Biology Lab, Duke Kunshan University, Kunshan, China. jianbo.yue@duke.edu.
  • # Contributed equally.
PMID: 38273307 DOI: 10.1186/s12915-024-01819-y
Abstract

Background: Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus Infection remains elusive.

Results: Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein-protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and Dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), Infection by preventing the escape of RNA genome from endocytic vesicles.

Conclusions: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).

Keywords

CapZ; Early endosomes; Endosomal trafficking; Virus entry; Virus infection.

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