Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/230885
Title: REDUCED CASPASE-1 ACTIVITY AND IL-1β CLEAVAGE CONTRIBUTE TO MULTILEVEL DAMPENING OF BAT INFLAMMASOME ACTIVATION
Authors: GOH XUE QIN, GERALDINE (WU XUEQIN)
ORCID iD:   orcid.org/0000-0003-2370-6287
Keywords: bats, caspase-1, AIM2, IL-1β, inflammasome
Issue Date: 28-Jul-2020
Citation: GOH XUE QIN, GERALDINE (WU XUEQIN) (2020-07-28). REDUCED CASPASE-1 ACTIVITY AND IL-1β CLEAVAGE CONTRIBUTE TO MULTILEVEL DAMPENING OF BAT INFLAMMASOME ACTIVATION. ScholarBank@NUS Repository.
Abstract: Bats have emerged as reservoir hosts for diverse lethal zoonotic viruses such as the recent SARS-CoV-2, yet suffer minimal clinical disease from these pathogens. Recent studies have found that multiple sensors of the innate immune inflammasome pathway are dampened in bats, including a complete genomic loss of AIM2 and reduced NLRP3 activation. Our study investigated the functional implications of absent AIM2 sensor in bats via its reconstitution in a bat cellular environment. We observed that the downstream caspase-1 activation, cell death and IL-1β secretion were not induced despite AIM2 restoration and ASC speck formation, and therefore hypothesized that caspase-1 and/or IL-1β were deficient in bats. Two key residues from caspase-1 of Pteropus bat were identified to be responsible for the abrogation of its activity, which is restored by substitution with the equivalent human caspase-1 amino acid residues. In contrast, in another bat (Myotis davdii) with intact caspase-1 activity, non-synonymous substitutions in the downstream substrate IL-1β resulted in its deficient cleavage and secretion. Thus, this study reports novel strategies targeting multiple levels of the inflammasome pathway with which bats have evolved to diminish activation and signaling.
URI: https://scholarbank.nus.edu.sg/handle/10635/230885
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