Abstract

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.

Details

Title
A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV
Author
Fan, Changfa 1 ; Wu, Xi 1 ; Liu, Qiang 2 ; Li, Qianqian 2 ; Liu, Susu 1 ; Lu, Jianjun 3 ; Yang, Yanwei 3 ; Cao, Yuan 1 ; Huang, Weijin 2 ; Liang, Chunnan 1 ; Tianlei Ying 4 ; Jiang, Shibo 4 ; Wang, Youchun 2   VIAFID ORCID Logo 

1  Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China; [email protected] (C.F.); [email protected] (X.W.); [email protected] (S.L.); [email protected] (Y.C.); [email protected] (C.L.) 
2  Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China; [email protected] (Q.L.); [email protected] (Q.L.); [email protected] (W.H.) 
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; [email protected] (J.L.); [email protected] (Y.Y.) 
4  Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai 200032, China; [email protected] (T.Y.); [email protected] (S.J.) 
First page
448
Publication year
2018
Publication date
2018
Publisher
MDPI AG
e-ISSN
19994915
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.3390/v10090448
ProQuest document ID
3177714194
Copyright
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.