A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 05 2023
25 05 2023
Historique:
received:
21
10
2022
accepted:
15
05
2023
medline:
29
5
2023
pubmed:
26
5
2023
entrez:
25
5
2023
Statut:
epublish
Résumé
Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing a role for an accessory protein in this context.
Identifiants
pubmed: 37230979
doi: 10.1038/s41467-023-38783-0
pii: 10.1038/s41467-023-38783-0
pmc: PMC10211296
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3026Subventions
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007180
Pays : United States
Organisme : NIH HHS
ID : S10 OD021747
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143639
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI141759
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143861
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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