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Updated: Jul 6, 2026

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Piezo1 inhibition promoted MELK degradation and impeded influenza virus entry into host cells
Jianfu He1, Huiyi Guo1, Kunyu Lu1
1Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, Guangdong Province Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Introduction:
The influenza virus continues to represent a persistent and significant challenge to public health worldwide. Viral entry into host cells is a critical initial step in the viral life cycle; however, the regulatory network of host factors involved in this process, particularly the role of Piezo-mechanosensitive elements, has not been fully elucidated.
Objectives:
To determine the precise role of Piezo1 in respiratory epithelial cells during influenza virus infection and to validate the antiviral efficacy of targeting Piezo1 in vivo.
Methods:
This study elucidated the molecular mechanism of Piezo1-MELK axis-mediated influenza virus entry into host cells via gene editing, proteomics, and IP-MS screening, and verified the anti-influenza effect of Piezo1 targeting in knockout mouse models.
Results:
We found that Piezo-type mechanosensitive ion channel component 1 (Piezo1) is crucial for IAV entry. Mechanistically, Piezo1 stabilizes the maternal embryonic leucine zipper kinase (MELK), which we identify as a novel IAV endocytic receptor that binds viral hemagglutinin (HA). Additionally, the influenza virus, through MELK, interacted with Piezo1, leading to calcium influx and F-actin polymerization, which drive influenza virus entry. Importantly, specifically inhibiting or knocking out Piezo1 in the lungs of mice significantly improves survival during influenza virus infection.
Conclusion:
This study reveals a Piezo1-MELK axis coordinating IAV attachment and endocytosis, suggesting that targeting Piezo1 could be a promising host-directed antiviral strategy.
Insights
Scientists discovered that Piezo1, a mechanosensitive channel, is essential for influenza virus entry. Targeting Piezo1 in mice improved survival, suggesting it as a novel antiviral strategy.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Influenza virus poses a significant global public health threat.
- Understanding host factors in viral entry is crucial for developing antivirals.
- The role of mechanosensitive channels like Piezo1 in influenza infection is not well understood.
Purpose of the Study:
- To investigate the function of Piezo1 in respiratory epithelial cells during influenza A virus (IAV) infection.
- To validate Piezo1 as a therapeutic target for influenza in vivo.
Main Methods:
- Utilized gene editing, proteomics, and IP-MS screening to elucidate the Piezo1-MELK axis.
- Employed knockout mouse models to assess the in vivo anti-influenza effects of Piezo1 targeting.
Main Results:
- Piezo1 is critical for IAV entry into host cells.
- Piezo1 stabilizes MELK, a novel IAV endocytic receptor that binds viral hemagglutinin (HA).
- Inhibition or knockout of Piezo1 in mouse lungs significantly enhances survival rates during influenza infection.
Conclusions:
- A novel Piezo1-MELK axis regulates IAV attachment and endocytosis.
- Targeting Piezo1 represents a promising host-directed antiviral strategy against influenza.
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