A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.
A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.
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DOI：
10.1038/s41467-023-38783-0
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发表时间：
2023-05-25
影响因子：
16.6
通讯作者：
Dittmann, Meike
中科院分区：
文献类型：
--
作者：
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
小动物模型一直是SARS-CoV-2传播研究的一个挑战，大多数研究人员使用金黄色仓鼠或雪貂。小鼠具有低成本、广泛可用性、较少的监管和饲养挑战以及存在多功能试剂和遗传工具箱的优点。然而，成年小鼠不会稳健地传播SARS-CoV-2。在这里，我们建立了一个模型的基础上新生小鼠，允许临床SARS-CoV-2分离株的传播。我们表征了祖先WA-1与变体α（B.1.1.7）、β（B.1.351）、γ（P.1）、δ（B.1.617.2）、Omicron BA.1和Omicron BQ.1.1相比的向性、呼吸道复制和传播。我们确定了从指数小鼠，这两个形状传输到接触小鼠的传染性颗粒脱落的时间和幅度的变异间差异。此外，我们表征了两种缺乏ORF 6或ORF 8宿主拮抗剂的重组SARS-CoV-2。ORF 8的去除将病毒复制转移到下呼吸道，导致我们模型中的传播显着延迟和减少。我们的研究结果表明，我们的新生小鼠模型的特点SARS冠状病毒-2传播的病毒和宿主决定因素的潜力，同时揭示了在这种情况下的辅助蛋白的作用。在这里，作者开发了SARS-CoV-2传播的新生小鼠模型，表征了病毒复制和关注变体脱落的差异，并表明ORF 8的缺失将病毒复制转移到下呼吸道并延迟传播。
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.
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影响因子：
6.4
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
DOI：
10.1038/s41579-021-00535-6
发表时间：
2021-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Leung NHL
通讯作者：
Leung NHL
影响因子：
5.4
作者：
Kopecky-Bromberg, Sarah A.;Martinez-Sobrido, Luis;Palese, Peter
通讯作者：
Palese, Peter
影响因子：
7.7
作者：
Bayarri-Olmos R;Johnsen LB;Idorn M;Reinert LS;Rosbjerg A;Vang S;Hansen CB;Helgstrand C;Bjelke JR;Bak-Thomsen T;Paludan SR;Garred P;Skjoedt MO
通讯作者：
Skjoedt MO