Characterization of Two Heterogeneous Lethal Mouse-Adapted SARS-CoV-2 Variants Recapitulating Representative Aspects of Human COVID-19.
Characterization of Two Heterogeneous Lethal Mouse-Adapted SARS-CoV-2 Variants Recapitulating Representative Aspects of Human COVID-19.
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DOI：
10.3389/fimmu.2022.821664
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发表时间：
2022
影响因子：
7.3
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Yan F;Li E;Wang T;Li Y;Liu J;Wang W;Qin T;Su R;Pei H;Wang S;Feng N;Zhao Y;Yang S;Xia X;Gao Y
新出现的严重急性呼吸综合征2型（SARS-CoV-2）已经引起了全球性的流行。2019冠状病毒病（COVID-19）的几种动物模型已被开发并应用于抗病毒研究。在这项研究中，两个致命的小鼠适应的SARS-CoV-2变异体（BMA 8和C57 MA 14）具有不同的毒力，从不同的主机，其特征是高病毒复制滴度在上呼吸道和下呼吸道，肺部病理，细胞因子风暴，细胞嗜性，淋巴细胞减少症，嗜中性粒细胞。两种变体在小鼠中表现出宿主遗传相关和年龄依赖性的发病率和死亡率，精细地反映了无症状、中度和重度COVID-19患者的临床表现。值得注意的是，这两种变体同样削弱了来自COVID-19恢复期的血清的中和能力，但C57 MA 14变体在体外显示出比BMA 8变体高得多的毒力。BMA 8和C57 MA 14变体的受体结合结构域（RBD）中的Q489 H取代导致SARS-CoV-2的受体从人血管紧张素转换酶2（hACE 2）转换为鼠血管紧张素转换酶2（mACE 2）。此外，在我们的研究中首次报道了E蛋白的A22 D和A36 V突变，这可能是导致两种变体之间毒力差异的原因。值得注意的是，使用BMA 8或C57 MA 14感染的老年小鼠模型验证了新型细菌样颗粒（BLP）候选疫苗的保护效力。BMA 8变异体和C57 MA 14变异体感染模型为评估疫苗和新治疗方法的功效提供了相对便宜且可获得的评估平台。这将促进对SARS-CoV-2传播和致病机制的进一步研究。
New emerging severe acute respiratory syndrome 2 (SARS-CoV-2) has caused a worldwide pandemic. Several animal models of coronavirus disease 2019 (COVID-19) have been developed and applied to antiviral research. In this study, two lethal mouse-adapted SARS-CoV-2 variants (BMA8 and C57MA14) with different virulence were generated from different hosts, which are characterized by high viral replication titers in the upper and lower respiratory tract, pulmonary pathology, cytokine storm, cellular tropism, lymphopenia, and neutrophilia. Two variants exhibit host genetics-related and age-dependent morbidity and mortality in mice, exquisitely reflecting the clinical manifestation of asymptomatic, moderate, and severe COVID-19 patients. Notably, both variants equally weaken the neutralization capacity of the serum derived from COVID-19 convalescent, but the C57MA14 variant showed a much higher virulence than the BMA8 variant in vitro. Q489H substitution in the receptor-binding domain (RBD) of BMA8 and C57MA14 variants results in the receptors of SARS-CoV-2 switching from human angiotensin-converting enzyme 2 (hACE2) to murine angiotensin-converting enzyme 2 (mACE2). Additionally, A22D and A36V mutation in E protein were first reported in our study, which potentially contributed to the virulence difference between the two variants. Of note, the protective efficacy of the novel bacterium-like particle (BLP) vaccine candidate was validated using the BMA8- or C57MA14-infected aged mouse model. The BMA8 variant- and C57MA14 variant-infected models provide a relatively inexpensive and accessible evaluation platform for assessing the efficacy of vaccines and novel therapeutic approaches. This will promote further research in the transmissibility and pathogenicity mechanisms of SARS-CoV-2.
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DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
影响因子：
4.7
作者：
Li, Entao;Chi, Hang;Xia, Xianzhu
通讯作者：
Xia, Xianzhu
DOI：
10.1016/j.ijid.2020.11.198
发表时间：
2021-03
期刊：
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子：
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作者：
Alsharidah S;Ayed M;Ameen RM;Alhuraish F;Rouheldeen NA;Alshammari FR;Embaireeg A;Almelahi M;Adel M;Dawoud ME;Aljasmi MA;Alshammari N;Alsaeedi A;Al-Adsani W;Arian H;Awad H;Alenezi HA;Alzafiri A;Gouda EF;Almehanna M;Alqahtani S;Alshammari A;Askar MZ
通讯作者：
Askar MZ
影响因子：
30.3
作者：
Kim, Young-Il;Kim, Seong-Gyu;Choi, Young Ki
通讯作者：
Choi, Young Ki