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

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 recombinan...

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Bibliographic Details
Published in:Nature communications 2024-01, Vol.15 (1), p.889-14, Article 889
Main Authors: Shi, Guoli, Li, Tiansheng, Lai, Kin Kui, Johnson, Reed F., Yewdell, Jonathan W., Compton, Alex A.
Format: Article
Language:English
Subjects:
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14/19
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Adaptive immunity
COVID-19
Epithelial cells
Epithelium
Humanities and Social Sciences
Infectivity
Interferon
Matrix metalloproteinase
Matrix metalloproteinases
Membrane fusion
multidisciplinary
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
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Summary: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. Shi and Li et al. show that SARS-CoV-2 Omicron subvariants have increased capacity to infect primary human nasal tissue using a distinct entry route that depends on matrix metalloproteinases as opposed to TMPRSS2 used by previous variants, which enables evasion from antiviral factors.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45075-8