UNIGE document Scientific Article
previous document  unige:161421  next document
add to browser collection
Title

Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta

Authors
Ulrich, Lorenz
Halwe, Nico Joel
Taddeo, Adriano
Ebert, Nadine
Schön, Jacob
Devisme, Christelle
Trüeb, Bettina Salome
Hoffmann, Bernd
show hidden authors show all authors [1 - 42]
Published in Nature. 2022, vol. 602, no. 7896, p. 307-313
Abstract

Emerging 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-S614Gin 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-S614Gshowed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614Gin 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-S614Gin naive animals.

Data Availability Statement: Sequence data are available on the NCBI Sequence Read Archive (SRA) under the accession numbers <a href="http://www.ncbi.nlm.nih.gov/sra?term=PRJEB45736" rel="noopener noreferrer" target="_blank">PRJEB45736</a> and <a href="http://www.ncbi.nlm.nih.gov/sra?term=PRJNA784099" rel="noopener noreferrer" target="_blank">PRJNA784099</a>, or in GenBank under the accession numbers <a href="https://www.ncbi.nlm.nih.gov/nuccore/MT108784" rel="noopener noreferrer" target="_blank">MT108784</a>, <a href="https://www.ncbi.nlm.nih.gov/nuccore/MZ433432" rel="noopener noreferrer" target="_blank">MZ433432</a>, <a href="https://www.ncbi.nlm.nih.gov/nuccore/OL675863" rel="noopener noreferrer" target="_blank">OL675863</a>, <a href="https://www.ncbi.nlm.nih.gov/nuccore/OL689430" rel="noopener noreferrer" target="_blank">OL689430</a> and <a href="https://www.ncbi.nlm.nih.gov/nuccore/OL689583" rel="noopener noreferrer" target="_blank">OL689583</a> as shown in Extended Data Table <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828469/table/Tab1/" rel="noopener noreferrer" target="_blank">?Table11</a>. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828469/#Sec26" rel="noopener noreferrer" target="_blank">Source data</a> are provided with this paper.

Keywords Amino Acid SubstitutionAngiotensin-Converting Enzyme 2 / geneticsAngiotensin-Converting Enzyme 2 / metabolismAnimalsAnimals, Laboratory / virologyCOVID-19 / transmissionCOVID-19 / veterinaryCOVID-19 / virologyCricetinaeDisease Models, AnimalEpithelial Cells / virologyFemaleFerrets / virologyHumansMaleMesocricetus / virologyMiceMice, TransgenicMutationSARS-CoV-2 / classificationSARS-CoV-2 / geneticsSARS-CoV-2 / growth & developmentSARS-CoV-2 / physiologySpike Glycoprotein, Coronavirus / geneticsSpike Glycoprotein, Coronavirus / metabolismVirulence / geneticsVirus Replication
Identifiers
PMID: 34937050
PMCID: PMC8828469
Full text
Article (Published version) (9.8 MB) - public document Free access
Supplemental data - Table 1 (21 Kb) - public document Free access
Supplemental data - Table 2 (13 Kb) - public document Free access
Appendix (131 Kb) - public document Free access
Appendix (136 Kb) - public document Free access
Appendix (139 Kb) - public document Free access
Appendix (167 Kb) - public document Free access
Appendix (206 Kb) - public document Free access
Appendix (128 Kb) - public document Free access
Appendix (57 Kb) - public document Free access
Appendix (118 Kb) - public document Free access
Appendix (99 Kb) - public document Free access
Appendix (185 Kb) - public document Free access
Appendix (73 Kb) - public document Free access
Appendix (191 Kb) - public document Free access
Appendix (83 Kb) - public document Free access
Appendix (131 Kb) - public document Free access
Appendix (72 Kb) - public document Free access
Appendix (112 Kb) - public document Free access
Appendix (88 Kb) - public document Free access
Appendix (78 Kb) - public document Free access
Other version: https://www.nature.com/articles/s41586-021-04342-0
Dataset: https://www.nature.com/articles/s41586-021-04342-0#Sec26
Structures
Research groups Emerging viruses (993)
Groupe Laurent Kaiser (virologie clinique) (668)
Projects
Swiss National Science Foundation: 31CA30_196062
Swiss National Science Foundation: 31CA30_196644
Swiss National Science Foundation: 310030_173085
Swiss National Science Foundation: 310030_179260
Swiss National Science Foundation: 31CA30_196383
European Commission: HONOURs
European Commission: RECoVER
European Commission: VEO
Deutsche Forschungsgemeinschaft (DFG): 453012513
German Ministry of Research: 01KI2021
Fondation Ancrage Bienfaisance du Groupe Pictet
Fondation Privée des Hôpitaux Universitaires de Genève
Citation
(ISO format)
ULRICH, Lorenz et al. Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta. In: Nature, 2022, vol. 602, n° 7896, p. 307-313. doi: 10.1038/s41586-021-04342-0 https://archive-ouverte.unige.ch/unige:161421

427 hits

85 downloads

Update

Deposited on : 2022-06-14

Export document
Format :
Citation style :