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LY6E is a pan-coronavirus restriction factor in the respiratory tract

Katrina B Mar1, Alexandra I Wells1, Marley C Caballero Van Dyke1

  • 1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Nature Microbiology
|July 13, 2023
PubMed

Insights

The antiviral protein LY6E protects against coronavirus infections. Specific cell types expressing LY6E are crucial for controlling airway infections by murine coronavirus and SARS-CoV-2.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • LY6E acts as an antiviral restriction factor, inhibiting coronavirus spike-mediated membrane fusion.
  • The specific cell types requiring LY6E for protection against respiratory coronavirus infections in vivo remain unidentified.

Purpose of the Study:

  • To identify LY6E-expressing cells critical for controlling airway infections by murine coronavirus and SARS-CoV-2.
  • To elucidate the role of LY6E in cellular resistance to coronavirus infection.

Main Methods:

  • Utilized a panel of seven conditional Ly6e knockout mouse models.
  • Assessed susceptibility to murine coronavirus and SARS-CoV-2 infection following targeted Ly6e deletion in specific cell populations.
  • Analyzed viral burden, clinical disease, and transcriptomic changes in lung epithelial cells.

Main Results:

  • Loss of LY6E in Lyz2+, Vav1+, and non-hematopoietic cells increased susceptibility to murine coronavirus.
  • Global Ly6e deficiency led to increased SARS-CoV-2 viral burden and clinical disease, with minimal immunopathology.
  • LY6E expression protected secretory club and ciliated cells from SARS-CoV-2 and preserved lung epithelial cell transcriptomic signatures.

Conclusions:

  • Lineage-restricted LY6E expression, rather than broad expression, is sufficient for conferring resistance to murine and human coronaviruses.
  • Specific cell types, including secretory club and ciliated cells, rely on LY6E for protection against SARS-CoV-2.
  • LY6E plays a vital role in host defense against respiratory coronavirus infections.

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