1. Generation of self-replicating airway organoids from the cave nectar bat Eonycteris spelaea as a model system for studying host–pathogen interactions in the bat airway epithelium
- Author
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Louisa L.Y. Chan, Akshamal M. Gamage, Chee Wah Tan, Kai Sen Tan, Jing Liu, Douglas Jie Wen Tay, Randy Jee Hiang Foo, Laurent Rénia, De Yun Wang, Lin-Fa Wang, Lee Kong Chian School of Medicine (LKCMedicine), and A*STAR Infectious Diseases Labs
- Subjects
Infectious Diseases ,Epidemiology ,Chiroptera ,Virology ,Drug Discovery ,Immunology ,Bat ,Medicine [Science] ,Parasitology ,General Medicine ,Microbiology - Abstract
Bats are reservoir hosts for various zoonotic viruses with pandemdic potential in humans and livestock. In vitro systems for studying bat host-pathogen interactions are of significant interest. Here, we establish protocols to generate bat airway organoids (AOs) and airway epithelial cells differentiated at the air-liquid interface (ALI-AECs) from tracheal tissues of the cave-nectar bat Eonycteris spelaea. In particular, we describe steps which enable laboratories that do not have access to live bats to perform extended experimental work upon procuring an initial batch of bat primary airway tissue. Complete mucociliary differentiation required treatment with IL-13. E. spelaea ALI-AECs supported productive infection with PRV3M, an orthoreovirus for which Pteropodid bats are considered the reservoir species. However, these ALI-AECs did not support SARS-CoV-2 infection, despite E. spelaea ACE2 receptor being capable of mediating SARS-CoV-2 spike pseudovirus entry. This work provides critical model systems for assessing bat species-specific virus susceptibility and the reservoir likelihood for emerging infectious agents. Ministry of Education (MOE) Nanyang Technological University National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research was funded in part by Singapore National Research Foundation (NRF2012NRF-CRP001-056, NRF2016NRF-NSFC002-013), the Singapore National Medical Research Council of Singapore (MOH-COV-ID19RF2-0001, MOH-COVID19RF-003, MOH-OFIRG19-MAY-0011, MOH-OFIRG10NOV-0050) and the Ministry of Education Singapore (MOE2019-T2-2-130); Singapore National Medical Research Council Centre Grant Program – Diabetes, Tuberculosis and Neuroscience No.CGAug16M009; the NUS Reimagine Research Grant, Singapore; and the Nanyang Technological University Lee Kong Chian School of Medicine LEARN grant (021914-00001).LLYC is supported by the Lee Kong Chian School of Medi-cine, Nanyang Technological University under the Dean’s Postdoctoral Fellowship and the Wong Peng Onn Fellow-ship (002823-00001).
- Published
- 2022