Article ; Online: Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus.
2019 Volume 93, Issue 6
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and ... ...
| Abstract | Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection. |
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| MeSH term(s) | Animals ; Cell Line ; Chlorocebus aethiops ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Cytokines/metabolism ; Dipeptidyl Peptidase 4/metabolism ; Disease Models, Animal ; Female ; Lung/virology ; Macrophages/metabolism ; Macrophages/virology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Respiratory Tract Infections/metabolism ; Respiratory Tract Infections/virology ; Vero Cells |
| Chemical Substances | Cytokines ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2019-03-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 80174-4 |
| ISSN | 1098-5514 ; 0022-538X |
| ISSN (online) | 1098-5514 |
| ISSN | 0022-538X |
| DOI | 10.1128/JVI.01818-18 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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