A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.

التفاصيل البيبلوغرافية
العنوان: A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.
المؤلفون: Rodriguez-Rodriguez BA, Ciabattoni GO, Duerr R, Valero-Jimenez AM, Yeung ST, Crosse KM, Schinlever AR, Bernard-Raichon L, Rodriguez-Galvan JJ, McGrath ME, Vashee S, Xue Y, Loomis C, Khanna KM, Cadwell K, Desvignes L, Frieman MF, Ortigoza MB, Dittmann M
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 24. Date of Electronic Publication: 2023 Mar 24.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets 1, 2 . 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 3 . 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 for the first time a role for an accessory protein in this context.
التعليقات: Update in: Nat Commun. 2023 May 25;14(1):3026. (PMID: 37230979)
معلومات مُعتمدة: R01 AI143861 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20221014 Latest Revision: 20230612
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9558433
DOI: 10.1101/2022.10.04.510658
PMID: 36238716
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2022.10.04.510658