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SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity

Liying Wang1,2, Chao Liu1,2, Bo Yang3

  • 1Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.

The Journal of Cell Biology
|June 8, 2022
PubMed

Insights

The SARS-CoV-2 virus

Area of Science:

  • Molecular biology
  • Virology
  • Cell biology

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19.
  • Loss of smell and taste are common COVID-19 symptoms potentially linked to cilia dysfunction.

Purpose of the Study:

  • To investigate the mechanism by which SARS-CoV-2 ORF10 protein causes cilia dysfunction.
  • To identify the molecular players involved in SARS-CoV-2-induced cilia impairment.

Main Methods:

  • Investigated the interaction between SARS-CoV-2 ORF10 and the CUL2ZYG11B complex.
  • Assessed the effect of ORF10 on E3 ligase activity and protein ubiquitination.
  • Examined the degradation of intraflagellar transport (IFT) complex B protein, IFT46.
  • Utilized hACE2 mice and primary human nasal epithelial cells (HNECs) to study cilia function.

Main Results:

  • SARS-CoV-2 ORF10 enhances CUL2ZYG11B E3 ligase activity by interacting with ZYG11B.
  • This leads to increased ubiquitination and proteasome-mediated degradation of IFT46.
  • SARS-CoV-2 ORF10 expression in human nasal cells and mouse respiratory tracts causes cilia dysfunction and loss of the ciliary layer.

Conclusions:

  • SARS-CoV-2 ORF10 hijacks the CUL2ZYG11B complex to degrade IFT46, impairing cilia biogenesis and maintenance.
  • This mechanism provides an etiological explanation for cilia-dysfunction-related symptoms in COVID-19.

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