Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids.
Signal Transduct Target Ther
; 7(1): 392, 2022 12 19.
Article
in English
| MEDLINE | ID: covidwho-2185768
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(IC) 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
Chiroptera
/
COVID-19
Limits:
Animals
/
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2022
Document Type:
Article
Affiliation country:
S41392-022-01247-w
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