Middle East Respiratory Syndrome-Coronavirus Infection into Established hDPP4-Transgenic Mice Accelerates Lung Damage Via Activation of the Pro-Inflammatory Response and Pulmonary Fibrosis.
J Microbiol Biotechnol
; 30(3): 427-438, 2020 Mar 28.
Article
in English
| MEDLINE | ID: covidwho-2163802
ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Coronavirus Infections
/
Dipeptidyl Peptidase 4
/
Middle East Respiratory Syndrome Coronavirus
/
Lung
Type of study:
Prognostic study
Topics:
Long Covid
/
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
J Microbiol Biotechnol
Year:
2020
Document Type:
Article
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