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SARS-CoV-2 Omicron subvariants progressively adapt to human cells with altered host cell entry
Yasuteru Sakurai1,2,3, Sayaka Okada2, Takehiro Ozeki2,4
1Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
Msphere
|August 27, 2024
Summary
The Omicron variant of SARS-CoV-2 adapts to human cells by using endosomes for entry, unlike the Delta variant. This ongoing adaptation influences its transmissibility and immune evasion, impacting global infections.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously evolves, with Omicron subvariants showing high transmissibility and immune escape.
- Understanding the virological features of emerging SARS-CoV-2 variants is crucial for predicting infections and developing antiviral strategies.
Purpose of the Study:
- To compare the entry mechanisms and cellular adaptation of SARS-CoV-2 Omicron subvariants (BA.1-BA.5, BA.2.75, XBB/BQ) with the Delta variant in human airway and intestinal cells.
- To investigate the evolutionary changes in host cell entry pathways and spike protein cleavage efficacy.
Main Methods:
- In vitro analysis of viral entry and replication in human upper/lower airway and intestinal cell models.
- Comparative assessment of host cell entry routes (cell-surface vs. endosomal) and protease dependence (TMPRSS2 vs. Cathepsin L).
- Evaluation of S1/S2 spike protein cleavage efficiency across different SARS-CoV-2 variants.
Main Results:
- Omicron subvariants demonstrated enhanced growth capability compared to earlier strains.
- Nasal epithelial cells supported efficient entry of certain Omicron subvariants, similar to Delta.
- All Omicron variants utilized endosomal cathepsin L for entry, differing from Delta's reliance on cell-surface TMPRSS2.
- Recent Omicron variants showed improved S1/S2 spike cleavage efficacy compared to earlier Omicron spikes.
Conclusions:
- The Omicron variant progressively adapts to human cells via endosome-mediated entry, a conserved mechanism across subvariants.
- Altered host cell entry pathways and improved spike cleavage contribute to the evolutionary success of Omicron subvariants.
- This study highlights both conserved and changing features of SARS-CoV-2 evolution, particularly regarding host cell interaction.
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