+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus



Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus



Journal of Virology 93(6):



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.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 066075173

Download citation: RISBibTeXText

PMID: 30626685


Related references

Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus. Plos one 10(12): E0145561, 2015

Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease. Journal of Infectious Diseases 219(5): 829-835, 2019

Middle East Respiratory Syndrome Coronavirus Causes Multiple Organ Damage and Lethal Disease in Mice Transgenic for Human Dipeptidyl Peptidase 4. Journal of Infectious Diseases 213(5): 712-722, 2016

Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. Journal of Virology 88(9): 5195-5199, 2014

Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus. Virology 518: 324-327, 2018

Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus. Virology 518: 324-327, 2018

Co-localization of Middle East respiratory syndrome coronavirus (MERS-CoV) and dipeptidyl peptidase-4 in the respiratory tract and lymphoid tissues of pigs and llamas. Transboundary and Emerging Diseases 66(2): 831-841, 2019

Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. Journal of Virology 88(16): 9220-9232, 2014

Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. Journal of Infectious Diseases 218(2): 197-207, 2018

Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome. American Journal of Pathology 186(1): 78-86, 2016

Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus. Virology Journal 10: 304, 2013

Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants. Journal of Virology 91(19):, 2017

Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus. Journal of Virology 88(3): 1834-1838, 2014

Assessing the Detection of Middle East Respiratory Syndrome Coronavirus IgG in Suspected and Proven Cases of Middle East Respiratory Syndrome Coronavirus Infection. Viral Immunology 30(9): 649-653, 2017

Acute febrile respiratory infection symptoms in Australian Hajjis at risk of exposure to Middle East respiratory syndrome coronavirus. Medical Journal of Australia 199(7): 453, 2013