A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV
by
Changfa Fan 1,†, Xi Wu 1,†, Qiang Liu 2, Qianqian Li 2, Susu Liu 1, Jianjun Lu 3, Yanwei Yang 3, Yuan Cao 1, Weijin Huang 2, Chunnan Liang 1, Tianlei Ying 4, Shibo Jiang 4 and Youchun Wang 2,*
Changfa Fan 1,†, Xi Wu 1,†, Qiang Liu 2, Qianqian Li 2, Susu Liu 1, Jianjun Lu 3, Yanwei Yang 3, Yuan Cao 1, Weijin Huang 2, Chunnan Liang 1, Tianlei Ying 4, Shibo Jiang 4 and Youchun Wang 2,*
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.
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Keywords:
mouse model; hDPP4; MERS-CoV; pseudotyped virus; authentic virus
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MDPI and ACS Style
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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