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

Viruses
Changfa FanYouchun Wang

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.

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Citations

Oct 17, 2019·International Journal of Molecular Sciences·Sang Il KimJunho Chung
Mar 25, 2020·Emerging Microbes & Infections·Jianhui NieYouchun Wang
May 30, 2020·Viruses·Nadin YounesGheyath K Nasrallah
Aug 21, 2019·Frontiers in Microbiology·Chean Yeah YongWen Siang Tan
Apr 28, 2020·Laboratory animal research·Mee Sook ParkMan-Seong Park
Jul 25, 2019·Viruses·Fang Li, Lanying Du
Jul 28, 2020·Journal of Clinical Medicine·Chrysi KoliakiNikolaos Tentolouris
Oct 16, 2020·Expert Opinion on Pharmacotherapy·Syed Shahzad HasanMuhammad Abdul Hadi
Nov 5, 2020·Journal of Virology·Javier Gutierrez-AlvarezLuis Enjuanes

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Datasets Mentioned

BETA
AFS88936.1

Methods Mentioned

BETA
transfection
PCR
genotyping
phage display
dissection
transgenic

Software Mentioned

GENEWIZ
GraphPad Prism
Living Image
GraphPad

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