| Literature DB >> 35150638 |
Alba Escalera1, Ana S Gonzalez-Reiche2, Sadaf Aslam3, Ignacio Mena3, Manon Laporte3, Rebecca L Pearl3, Andrea Fossati4, Raveen Rathnasinghe1, Hala Alshammary5, Adriana van de Guchte2, Keith Farrugia2, Yiren Qin6, Mehdi Bouhaddou4, Thomas Kehrer1, Lorena Zuliani-Alvarez4, David A Meekins7, Velmurugan Balaraman7, Chester McDowell7, Jürgen A Richt7, Goran Bajic5, Emilia Mia Sordillo8, Marion Dejosez6, Thomas P Zwaka6, Nevan J Krogan9, Viviana Simon10, Randy A Albrecht3, Harm van Bakel11, Adolfo García-Sastre12, Teresa Aydillo13.
Abstract
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.Entities:
Keywords: H655Y mutation; SARS-CoV-2; fusion; gamma; omicron; spike cleavage; syncytia formation; variants of concern
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Year: 2022 PMID： 35150638 PMCID： PMC8776496 DOI： 10.1016/j.chom.2022.01.006
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 31.316