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
  • 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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