ArticleiScience2024
Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Pyroptosis- and Necroptosis-Related Signaling in Salicylate UV Absorber-Induced Toxicity: Implications for Sustainable Chemistry and Human Health.International journal of molecular sciences · 2026Article
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- The NSP5, ORF6 and NSP13 of SARS-CoV-2 Cooperate to Modulate Inflammatory Cell Death Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial dysfunction triggers Zbp1-mediated necroptosis and inflammation in acute lung injury.Biomolecules & biomedicine · 2025Article
- The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins.Open biology · 2025Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RHIM is a protein motif facilitating the assembly of large signaling complexes triggering regulated cell death. A few DNA viruses employ viral RHIMs mimicking host RHIMs and counteract cell death by interacting with host RHIM-proteins to alleviate antiviral defenses. Whether RNA viruses operate such viral RHIMs remains unknown. Here, we identified viral RHIMs in Nsp13 of SARS-CoV-2 and other bat RNA viruses, providing the basis for bats as the hosts for their evolution. Nsp13 promoted viral RHIM and RNA-binding channel-dependent cell death. However, Nsp13 viral RHIM is more critical for human cell death than in bat-derived Tb1 Lu cells, suggesting species-specific regulation. Nsp13 showed RHIM-dependent interactions with ZBP1 and RIPK3, forming large complexes and promoting ZBP1-RIPK3 signaling-mediated cell death. Intriguingly, the SARS-CoV-2 genome consisted of Z-RNA-forming segments promoting Nsp13-dependent cell death. Our findings reveal the functional viral RHIMs of bat-originated RNA viruses regulating host cell death associated with ZBP1-RIPK3 signaling, indicating possible mechanisms of cellular damage and cytokine storm in bat-originated RNA virus infections.
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