Bibliographic Details
| Title: |
A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8. |
| Authors: |
Rodriguez-Rodriguez, Bruno A., Ciabattoni, Grace O., Duerr, Ralf, Valero-Jimenez, Ana M., Yeung, Stephen T., Crosse, Keaton M., Schinlever, Austin R., Bernard-Raichon, Lucie, Rodriguez Galvan, Joaquin, McGrath, Marisa E., Vashee, Sanjay, Xue, Yong, Loomis, Cynthia A., Khanna, Kamal M., Cadwell, Ken, Desvignes, Ludovic, Frieman, Matthew B., Ortigoza, Mila B., Dittmann, Meike |
| Source: |
Nature Communications; 5/25/2023, Vol. 14 Issue 1, p1-15, 15p |
| Subject Terms: |
SARS-CoV-2, LABORATORY mice, GOLDEN hamster, ANIMAL disease models, MICE, SARS-CoV-2 Delta variant, SARS-CoV-2 Omicron variant |
| Abstract: |
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. Here the authors develop a neonatal mouse model for SARS-CoV-2 transmission, characterize differences in viral replication and shedding of variants of concerns, and show that deletion of ORF8 shifts viral replication to the lower respiratory tract and delays transmission. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
