2. Academic Validation
  3. Mechanosensation promotes broad-spectrum antiviral defense through membrane remodeling

Mechanosensation promotes broad-spectrum antiviral defense through membrane remodeling

  • Cell Chem Biol. 2026 Mar 19;33(3):307-320.e4. doi: 10.1016/j.chembiol.2026.01.004.
Yuehan Huang 1,  Haoran Guo 1,  Delong Gao 2,  Yubin Tang 1,  Jiaxin Yang 1,  Fushun Ni 1,  Ling Xue 1,  Huili Li 1,  Dongxue Liu 3,  Lili Zhang 4,  Qingran Yang 5,  Shijin Wang 1,  Xiao-Fang Yu 6,  Zhenglei Yu 2,  Junqi Niu 7,  Wei Wei 8
Affiliations

Affiliations

  • 1 Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
  • 2 The Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, Jilin 130012, China.
  • 3 Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin 130021, China; Department of Pathology, Medical College, Yanbian University, Yanji, Jilin 136200, China.
  • 4 Department of Ultrasound Diagnosis, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
  • 5 Department of Respiration, Children's Medical Center, First Hospital, Jilin University, Changchun, Jilin 130021, China.
  • 6 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • 7 Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China.
  • 8 Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin 130021, China; Cancer Center, Institute of Translational Medicine, Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: [email protected].
PMID: 41650963 DOI: 10.1016/j.chembiol.2026.01.004
Abstract

The capacity to sense mechanical stimuli represents one of the most fundamental characteristics of life, enabling organisms to navigate their environment. Here, we identify the mechano-antiviral response system (MARS), a Piezo1-mediated pathway that confers broad-spectrum Antiviral immunity distinct from known innate immune systems. Using Enterovirus D68 (EV-D68) as a model, we demonstrate that cellular compression or fluid pressure activates Piezo1-dependent Antiviral resistance in non-immune cells. Piezo1 functions as a natural Antiviral factor, and its pharmacological activation protects against multiple clinical isolates of EV-D68. Mechanistically, the activation of the biomechanical-Piezo1 axis results in a marked reduction in host cell membrane fluidity, a critical determinant for viral entry. Consequently, MARS restricts the replication of diverse viruses, including rhinovirus and influenza. In vivo studies reveal that Piezo1 agonists or mechanical stimuli alleviate EV-D68-induced neurological damage and lethality. Our findings underscore MARS-mediated membrane remodeling as a non-canonical Antiviral strategy, expanding the paradigms of immune stimulation.

Keywords

Piezo1; antiviral defense; biomechanic therapy; mechanical force; viral infection.

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