Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta
Author:
Ulrich LorenzORCID, Halwe Nico JoelORCID, Taddeo AdrianoORCID, Ebert Nadine, Schön Jacob, Devisme Christelle, Trüeb Bettina Salome, Hoffmann BerndORCID, Wider Manon, Fan Xiaoyu, Bekliz Meriem, Essaidi-Laziosi Manel, Schmidt Marie Luisa, Niemeyer DanielaORCID, Corman Victor MaxORCID, Kraft Anna, Godel Aurélie, Laloli Laura, Kelly Jenna N.ORCID, Calderon Brenda M., Breithaupt AngeleORCID, Wylezich ClaudiaORCID, Berenguer Veiga InêsORCID, Gultom Mitra, Osman Sarah, Zhou BinORCID, Adea Kenneth, Meyer BenjaminORCID, Eberhardt Christiane S., Thomann LisaORCID, Gsell Monika, Labroussaa FabienORCID, Jores JörgORCID, Summerfield Artur, Drosten ChristianORCID, Eckerle Isabella Anne, Wentworth David E.ORCID, Dijkman RonaldORCID, Hoffmann DonataORCID, Thiel VolkerORCID, Beer MartinORCID, Benarafa CharafORCID
Abstract
AbstractEmerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models—the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference36 articles.
1. Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409–424 (2021). 2. Tao, K. et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat. Rev. Genet. 22, 757–773 (2021). 3. Zhou, B. et al. SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 592, 122–127 (2021). 4. Korber, B. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812–827.e819 (2020). 5. Plante, J. A. et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature 592, 116–121 (2021).
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