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

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 differenti...

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Main Authors: Chan, Louisa L. Y., Gamage, Akshamal M., Tan, Chee Wah, Tan, Kai Sen, Liu, Jing, Tay, Douglas Jie Wen, Foo, Randy Jee Hiang, Rénia, Laurent, Wang, De Yun, Wang, Lin-Fa
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10356/164848
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author Chan, Louisa L. Y.
Gamage, Akshamal M.
Tan, Chee Wah
Tan, Kai Sen
Liu, Jing
Tay, Douglas Jie Wen
Foo, Randy Jee Hiang
Rénia, Laurent
Wang, De Yun
Wang, Lin-Fa
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Chan, Louisa L. Y.
Gamage, Akshamal M.
Tan, Chee Wah
Tan, Kai Sen
Liu, Jing
Tay, Douglas Jie Wen
Foo, Randy Jee Hiang
Rénia, Laurent
Wang, De Yun
Wang, Lin-Fa
author_sort Chan, Louisa L. Y.
collection NTU
description 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.
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spelling ntu-10356/1648482023-03-05T16:55:12Z 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 Chan, Louisa L. Y. Gamage, Akshamal M. Tan, Chee Wah Tan, Kai Sen Liu, Jing Tay, Douglas Jie Wen Foo, Randy Jee Hiang Rénia, Laurent Wang, De Yun Wang, Lin-Fa Lee Kong Chian School of Medicine (LKCMedicine) A*STAR Infectious Diseases Labs Science::Medicine Bat Chiroptera 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). 2023-02-20T05:32:51Z 2023-02-20T05:32:51Z 2023 Journal Article Chan, L. L. Y., Gamage, A. M., Tan, C. W., Tan, K. S., Liu, J., Tay, D. J. W., Foo, R. J. H., Rénia, L., Wang, D. Y. & Wang, L. (2023). 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. Emerging Microbes & Infections, 12(1), e2148561-. https://dx.doi.org/10.1080/22221751.2022.2148561 2222-1751 https://hdl.handle.net/10356/164848 10.1080/22221751.2022.2148561 36440480 2-s2.0-85144094299 1 12 e2148561 en NRF2012NRF-CRP001-056 NRF2016NRF-NSFC002-013 MOH-COV-ID19RF2-0001 MOH-COVID19RF-003 MOH-OFIRG19-MAY-0011 MOH-OFIRG10NOV-0050 MOE2019-T2-2-130 CGAug16M009 021914-00001 002823-00001 Emerging Microbes & Infections © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. application/pdf
spellingShingle Science::Medicine
Bat
Chiroptera
Chan, Louisa L. Y.
Gamage, Akshamal M.
Tan, Chee Wah
Tan, Kai Sen
Liu, Jing
Tay, Douglas Jie Wen
Foo, Randy Jee Hiang
Rénia, Laurent
Wang, De Yun
Wang, Lin-Fa
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Science::Medicine
Bat
Chiroptera
url https://hdl.handle.net/10356/164848
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