The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device

• Published in: Animal models and experimental medicine Vol. 2; no. 4; pp. 269 - 281
• Main Authors: Hao, Xin‐yan, Lv, Qi, Li, Feng‐di, Xu, Yan‐feng, Gao, Hong
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2019; John Wiley and Sons Inc; Wiley
• Subjects: Aerosols; animal nose‐only exposure device; animals; Antigens; brain; Chemokines; Coronaviridae; Coronavirus infections; Coronaviruses; Cytokines; Fatalities; genetically modified organisms; hDPP4 transgenic mice; Histopathology; Infections; Inflammation; intranasal instillation; Laboratory animals; Lesions; Lung diseases; lungs; medicine; MERS‐CoV aerosol infection; Middle East respiratory syndrome coronavirus; necropsy; Nose; Original; Pathogenesis; pneumonia; Public health; Respiratory diseases; Rodents; Survival; therapeutics; Transgenic animals; Transgenic mice; Vaccines; viral antigens; viral load; virus replication; Viruses; weight loss; Middle East; China; intranasal instillation; animal nose‐only exposure device; MERS‐CoV aerosol infection; hDPP4 transgenic mice
• ISSN: 2576-2095; 2096-5451; 2576-2095
• DOI: 10.1002/ame2.12088

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.