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. 2020 Jun 25;217(7):e20200885. doi: 10.1084/jem.20200885

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© 2020 Kesavardhana and Kanneganti

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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graphic file with name JEM_20200885_Fig2.jpg — Schematic representation of ZBP1 activation promoting cell death and inflammation. Z-RNAs from IAV or murine cytomegalovirus (MCMV) or dsRNAs formed by ERVs stimulate Zα domain–dependent activation of ZBP1. When RIPK1 is deleted in keratinocytes or the RHIM domain of RIPK1 is mutated, ERV-mediated activation of ZBP1 promotes RIPK3-MLKL–mediated necroptosis. Activation of ZBP1 by Z-RNAs from IAV triggers assembly of the PANoptosome, which engage pyroptosis, apoptosis, and necroptosis (PANoptosis). CARD, caspase activation and recruitment domain; CASP, caspase; DD, death domain; DED, death effector domain; LRR, leucine-rich repeat; PYD, pyrin domain.