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Article: Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids

TitleAnalogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids
Authors
Issue Date19-Dec-2022
PublisherSpringer Nature
Citation
Signal transduction and targeted therapy, 2022, v. 7, n. 1 How to Cite?
Abstract

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.


Persistent Identifierhttp://hdl.handle.net/10722/339637
ISSN
2023 Impact Factor: 40.8
2023 SCImago Journal Rankings: 8.737
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Xiaojuan-
dc.contributor.authorLi, Cun-
dc.contributor.authorWan, Zhixin-
dc.contributor.authorChiu, Man Chun-
dc.contributor.authorHuang, Jingjing-
dc.contributor.authorYu, Yifei-
dc.contributor.authorZhu, Hin-
dc.contributor.authorCai, Jian-Piao-
dc.contributor.authorRong, Lei-
dc.contributor.authorSong, You-qiang-
dc.contributor.authorChu, Hin-
dc.contributor.authorCai, Zongwei-
dc.contributor.authorJiang, Shibo-
dc.contributor.authorYuen, Kwok-yung-
dc.contributor.authorZhou, Jie-
dc.date.accessioned2024-03-11T10:38:10Z-
dc.date.available2024-03-11T10:38:10Z-
dc.date.issued2022-12-19-
dc.identifier.citationSignal transduction and targeted therapy, 2022, v. 7, n. 1-
dc.identifier.issn2095-9907-
dc.identifier.urihttp://hdl.handle.net/10722/339637-
dc.description.abstract<p>Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.<br></p>-
dc.languageeng-
dc.publisherSpringer Nature-
dc.relation.ispartofSignal transduction and targeted therapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAnalogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids-
dc.typeArticle-
dc.identifier.doi10.1038/s41392-022-01247-w-
dc.identifier.scopuseid_2-s2.0-85144329051-
dc.identifier.volume7-
dc.identifier.issue1-
dc.identifier.eissn2059-3635-
dc.identifier.isiWOS:000900125100001-
dc.identifier.issnl2059-3635-

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