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

Author:

Iwata-Yoshikawa Naoko1,Okamura Tadashi123,Shimizu Yukiko2,Kotani Osamu4,Sato Hironori4,Sekimukai Hanako15,Fukushi Shuetsu6,Suzuki Tadaki1,Sato Yuko1,Takeda Makoto7ORCID,Tashiro Masato8,Hasegawa Hideki1,Nagata Noriyo1

Affiliation:

1. Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan

2. Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

3. Section of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

4. Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan

5. Department of Tissue Physiology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan

6. Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan

7. Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan

8. Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan

Abstract

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.

Funder

Ministry of Health, Labour and Welfare

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Sports, Science and Technology

National Center for Global Health and Medicine

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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