Infection of Primary Nasal Epithelial Cells Differentiates Among Lethal and Seasonal Human Coronaviruses

The study titled “Infection of Primary Nasal Epithelial Cells Differentiates Among Lethal and Seasonal Human Coronaviruses” provides significant insights into how different human coronaviruses (HCoVs) interact with the nasal epithelium, which serves as the primary entry point and barrier for these viruses.

Here’s a detailed summary:

Study Overview

  • Objective: To understand how lethal (SARS-CoV-2 and MERS-CoV) and seasonal (HCoV-NL63 and HCoV-229E) HCoVs interact with primary human nasal epithelial cells.
  • Methods: Utilized primary human nasal epithelial cells grown at air–liquid interface to replicate the in vivo nasal epithelium.

Key Results

  1. Viral Replication:
    • All four HCoVs showed productive replication in nasal cultures.
    • SARS-CoV-2 replicated most robustly, with peak viral titers 10-fold higher than either MERS-CoV or HCoV-NL63​​.
  2. Impact of Temperature:
    • Replication of SARS-CoV-2 and HCoV-NL63, but not MERS-CoV, was modulated by temperature.
    • Seasonal HCoVs (HCoV-NL63 and -229E) showed attenuated replication at 37°C (lower airway temperature) compared to 33°C (upper airway temperature)​​.
  3. Cellular Tropism:
    • SARS-CoV-2 and HCoV-NL63 primarily infected ciliated cells, while MERS-CoV predominantly infected non-ciliated goblet cells.
    • This pattern is consistent with the cellular receptors used by these viruses (ACE2 for SARS-CoV-2 and HCoV-NL63, DPP4 for MERS-CoV)​​.
  4. Epithelial Barrier Integrity:
    • SARS-CoV-2 and HCoV-NL63 caused a reduction in epithelial barrier integrity, indicated by decreases in transepithelial electrical resistance (TEER).
    • MERS-CoV did not cause significant changes in epithelial barrier integrity​​.
  5. Cytotoxicity:
    • SARS-CoV-2 and HCoV-NL63 caused significant cytotoxicity in nasal epithelial cells, unlike MERS-CoV.
    • Cytotoxicity was measured using a lactate dehydrogenase (LDH) release assay​​.
  6. HCoV-229E:
    • HCoV-229E, another seasonal HCoV, also replicated productively and caused significant cytotoxicity in nasal cultures​​.
  7. Impact of IL-13 Treatment:
    • IL-13 treatment, used to mimic asthmatic airways, robustly influenced cellular distribution and HCoV receptor abundance.
    • MERS-CoV receptor DPP4 expression increased with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, was down-regulated.
    • IL-13 treatment enhanced MERS-CoV and HCoV-229E replication but reduced SARS-CoV-2 and HCoV-NL63 replication​​.

Significance

This study highlights the diverse interactions of HCoVs with the nasal epithelium, which can influence disease severity and transmissibility. Understanding these interactions is crucial for developing targeted interventions and treatments for different HCoVs, especially considering varying responses based on factors like temperature and pre-existing conditions (like asthma).

Conclusion

The study provides a comprehensive understanding of how different HCoVs behave in the nasal epithelium, offering insights into their pathogenicity and potential strategies for prevention and treatment. It underscores the importance of considering both the type of coronavirus and the individual’s nasal environment in understanding and managing HCoV infections.

Read More: https://www.pnas.org/doi/10.1073/pnas.2218083120

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