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A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV

1
Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China
2
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China
3
National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China
4
Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai 200032, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2018, 10(9), 448; https://doi.org/10.3390/v10090448
Received: 24 June 2018 / Revised: 13 August 2018 / Accepted: 17 August 2018 / Published: 23 August 2018
(This article belongs to the Special Issue MERS-CoV)
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. View Full-Text
Keywords: mouse model; hDPP4; MERS-CoV; pseudotyped virus; authentic virus mouse model; hDPP4; MERS-CoV; pseudotyped virus; authentic virus
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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. A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV. Viruses 2018, 10, 448.

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