| First Author | Fan C | Year | 2018 |
| Journal | Viruses | Volume | 10 |
| Issue | 9 | PubMed ID | 30142928 |
| Mgi Jnum | J:279060 | Mgi Id | MGI:6359298 |
| Doi | 10.3390/v10090448 | Citation | Fan C, et al. (2018) A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV. Viruses 10(9) |
| abstractText | 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. |
