<i>In vitro</i> and <i>in vivo</i> characterization of a bat merbecovirus with ACE2- and DPP4-independent cell entry
Betacoronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have caused three significant outbreaks in the past two decades and are believed to have originated from bats. To investigate the potential for future outbreaks, we generated a Japanese bat-derived MERS-related coronavirus, designated EjCoV-3, using reverse genetics. Our results showed that EjCoV-3 does not utilize ACE2 and DPP4, cell entry receptors for SARS-CoV and MERS-CoV, as a means of infection. However, we found that EjCoV-3 is the first bat merbecovirus capable of efficiently replicating in human respiratory cells and the respiratory tract of hamsters. These findings provide new insight into the potential for MERS-related coronaviruses that do not use ACE2 and DPP4 to infect the human respiratory tract, highlighting the importance of preparedness for outbreaks caused by these viruses.
Authors
- James Chambers (ORCID: https://orcid.org/0000-0001-5273-7221)
- Ayano Ichikawa
- Misa Katayama
- Taisuke Horimoto
- Naohiro Takahashi (ORCID: https://orcid.org/0000-0001-9431-9036)
- Kosuke Ohira
- Masayuki Shimojima (ORCID: https://orcid.org/0000-0002-5745-8413)
- Akiko Takenaka‐Uema (ORCID: https://orcid.org/0000-0002-6577-896X)
- Kazuyuki Uchida (ORCID: https://orcid.org/0000-0003-4823-0318)
- Hiromichi Matsugo (ORCID: https://orcid.org/0000-0002-4214-5254)
- Hiroho Ishida (ORCID: https://orcid.org/0000-0003-4314-199X)
- Wataru Sekine
- Shin Murakami (ORCID: https://orcid.org/0000-0003-0274-9165)
- Kaixin Li (ORCID: https://orcid.org/0000-0003-4496-5448)
- Tomoya Kitamura (ORCID: https://orcid.org/0000-0002-0251-7543)
Institutions
- National Agriculture and Food Research Organization (JP)
- National Institute of Infectious Diseases (JP)
- National Institute of Animal Health (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1128/jvi.00727-25
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Japan Agency for Medical Research and Development