Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue

Guoli Shi, Tiansheng Li, Kin Kui Lai, Reed F. Johnson, Jonathan W. Yewdell and Alex A. Compton ()
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Guoli Shi: Center for Cancer Research, National Cancer Institute
Tiansheng Li: National Institute of Allergy and Infectious Diseases
Kin Kui Lai: Center for Cancer Research, National Cancer Institute
Reed F. Johnson: National Institute of Allergy and Infectious Diseases
Jonathan W. Yewdell: National Institute of Allergy and Infectious Diseases
Alex A. Compton: Center for Cancer Research, National Cancer Institute

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, we show that mutations unique to Omicron Spike enable enhanced entry into nasal tissue. Unlike earlier variants of SARS-CoV-2, our findings suggest that Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. Furthermore, we demonstrate that this entry pathway unlocked by Omicron Spike enables evasion from constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.

Date: 2024
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DOI: 10.1038/s41467-024-45075-8

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