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Publication : The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device.

First Author  Hao XY Year  2019
Journal  Animal Model Exp Med Volume  2
Issue  4 Pages  269-281
PubMed ID  31942559 Mgi Jnum  J:286454
Mgi Id  MGI:6403677 Doi  10.1002/ame2.12088
Citation  Hao XY, et al. (2019) The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device. Animal Model Exp Med 2(4):269-281
abstractText  Background: Middle East respiratory syndrome coronavirus (MERS-CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health. Methods: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS-CoV by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues. Results: MERS-CoV aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-CoV instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-CoV aerosol-infected mice than in the MERS-CoV instillation-inoculated mice. Conclusion: hDPP4 transgenic mice were successfully infected with MERS-CoV aerosols via an animal nose-only exposure device, and aerosol- and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.
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