Journal
CELL HOST & MICROBE
Volume 30, Issue 3, Pages 373-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2022.01.006
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Funding
- CRIPT (Center for Research on Influenza Pathogenesis and Transmission)
- NIAID [75N93021C00014, U19AI135972, U19AI142733]
- NCI SeroNet grant [U54CA260560]
- DARPA [HR0011-19-2-0020]
- JPB Foundation
- Open Philanthropy Project [2020-215611 (5384)]
- NBAF Transition Funds from the State of Kansas
- NIAID Centers of Excellence for Influenza Research and Surveillance [HHSN 272201400006C]
- AMP Core of the Center for Emerging and Zoonotic Infectious Diseases of the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) [P20GM130448]
- Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases [HSHQDC 16-A-B0006]
- NIH [U19AI135972, U19AI135990]
- F. Hoffmann-La Roche
- Vir Biotechnology
- Marion Alban MSCIC Scholars Award
- 2020 Robin Chemers Neustein Postdoctoral fellowship
- Belgian American Education Foundation
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This study characterized the spike polymorphisms of the emerging SARS-CoV-2 variants and investigated their impact on transmissibility and virus pathogenicity. The findings showed that specific substitutions enhance viral replication and spike protein cleavage, leading to increased transmission efficiency in infection models and human airway systems.
SARS-CoV-2 lineages have diverged into highly prevalent variants termed variants of concern(VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S:655Y substitution was transmitted more efficiently than its ancestor S:655H in the hamster infection model and was able to outcompete S:655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.
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