A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV.
A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV.
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DOI：
10.3390/v10090448
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发表时间：
2018-08-23
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Fan C;Wu X;Liu Q;Li Q;Liu S;Lu J;Yang Y;Cao Y;Huang W;Liang C;Ying T;Jiang S;Wang Y
感染中东呼吸综合征冠状病毒（MERS-CoV）会导致呼吸道疾病，死亡率很高（约35%）。在生物安全三级（BSL-3）设施中处理病毒的要求阻碍了急需的抗病毒药物的开发。在此，我们利用CRISPR/Cas9技术将人二肽基肽酶4 （hDPP4）插入到Rosa26位点，建立了一种新的小鼠模型，在遗传稳定的小鼠品系中实现了该转基因的全局表达。小鼠对MERS-CoV临床毒株hCoV-EMC的感染高度敏感，该毒株可引起小鼠严重的弥漫性肺部疾病，并且也可被优化的MERS-CoV假型感染。给予中和性单克隆抗体H111-1和m336，以及融合抑制剂肽HR2P-M2，可以保护小鼠免受真型和假型MERS-CoV的攻击。这些结果证实，hdpp4敲入小鼠是在BSL-3和bsl -2设施中分别研究MERS-CoV发病机制和抗MERS-CoV抗病毒药物的新模型。
Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.
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影响因子：
56.3
作者：
Cauchemez, Simon;Fraser, Christophe;Van Kerkhove, Maria D.;Donnelly, Christi A.;Riley, Steven;Rambaut, Andrew;Enouf, Vincent;van der Werf, Sylvie;Ferguson, Neil M.
通讯作者：
Ferguson, Neil M.
使用人源化中和抗体进行单剂量治疗可以充分保护人类转基因小鼠模型免受致命的中东呼吸综合征（MERS）冠状病毒感染。
影响因子：
7.6
作者：
Qiu, Hongjie;Sun, Shihui;Xiao, He;Feng, Jiannan;Guo, Yan;Tai, Wanbo;Wang, Yufei;Du, Lanying;Zhao, Guangyu;Zhou, Yusen
通讯作者：
Zhou, Yusen
影响因子：
6.7
作者：
Falzarano D;de Wit E;Feldmann F;Rasmussen AL;Okumura A;Peng X;Thomas MJ;van Doremalen N;Haddock E;Nagy L;LaCasse R;Liu T;Zhu J;McLellan JS;Scott DP;Katze MG;Feldmann H;Munster VJ
通讯作者：
Munster VJ
DOI：
10.1073/pnas.1510199112
发表时间：
2015-08-18
影响因子：
11.1
作者：
Corti, Davide;Zhao, Jincun;Lanzavecchia, Antonio
通讯作者：
Lanzavecchia, Antonio
影响因子：
17.1
作者：
Luke, Thomas;Wu, Hua;Frieman, Matthew B.
通讯作者：
Frieman, Matthew B.