TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection

Author:

Iwata-Yoshikawa Naoko1,Okamura Tadashi23,Shimizu Yukiko2,Hasegawa Hideki1,Takeda Makoto4ORCID,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. Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan

Abstract

Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.

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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