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Influenza virus reduces ubiquitin E3 ligase MARCH10 expression to decrease ciliary beat frequency.

MuChun Tsai1, Rachael E Rayner2, Lexie Chafin1

  • 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|February 28, 2023
PubMed
Summary
This summary is machine-generated.

Influenza infection reduces MARCH10, a protein crucial for airway cilia function and immune defense. Restoring MARCH10 levels may protect against respiratory viral infections.

Keywords:
E3 ubiquitin ligaseMARCH10ciliainfluenzaubiquitination

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Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Respiratory viruses like influenza impair airway cilia function, compromising mucociliary clearance and immune defense.
  • Ubiquitination, mediated by E3 ligases, is vital for cilia assembly and disassembly.

Purpose of the Study:

  • To investigate the role of the membrane-associated RING-CH (MARCH) E3 ligase family in host defense during influenza infection.
  • To determine the specific function of MARCH10 in ciliated epithelial cells during viral respiratory infections.

Main Methods:

  • Examined MARCH10 expression in mice, human lung cells, and tissue during influenza infection.
  • Utilized CRISPR/Cas9 for MARCH10 depletion and studied its effects on ciliary function in differentiated human bronchial epithelial cells (HBECs).
  • Assessed the impact of MARCH10 manipulation on influenza hemagglutinin levels and IL-1β cytokine expression.

Main Results:

  • MARCH10 expression was significantly decreased during influenza infection across multiple models.
  • MARCH10 depletion reduced ciliary beat frequency and affected dynein axonemal intermediate chain 1 levels.
  • MARCH10 overexpression decreased influenza hemagglutinin, while knockdown increased IL-1β, indicating a regulatory role.

Conclusions:

  • MARCH10 plays a significant role in maintaining airway ciliary function and host defense against influenza.
  • MARCH10 exhibits a protective effect on pulmonary innate immunity during respiratory viral infections.
  • Targeting MARCH10 could be a potential therapeutic strategy for influenza and other respiratory viral diseases.