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

Autor: Liu X; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Li C; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Wan Z; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Chiu MC; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Huang J; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Yu Y; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Zhu L; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China., Cai JP; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Rong L; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China., Song YQ; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China.; School of Biomedical Sciences, State Key Laboratory of Brain and Cognitive Sciences, The University of Hongkong, Hong Kong, China., Chu H; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China., Cai Z; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China., Jiang S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China. shibojiang@fudan.edu.cn., Yuen KY; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. kyyuen@hku.hk.; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China. kyyuen@hku.hk.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China. kyyuen@hku.hk., Zhou J; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. jiezhou@hku.hk.; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China. jiezhou@hku.hk.; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China. jiezhou@hku.hk.
Jazyk: angličtina
Zdroj: Signal transduction and targeted therapy [Signal Transduct Target Ther] 2022 Dec 19; Vol. 7 (1), pp. 392. Date of Electronic Publication: 2022 Dec 19.
DOI: 10.1038/s41392-022-01247-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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