Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling

Mishra, S and Jain, D and Dey, AA and Nagaraja, S and Srivastava, M and Khatun, O and Balamurugan, K and Anand, M and Ashok, AK and Tripathi, S and Ganji, M and Kesavardhana, S (2024) Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling. In: iScience, 27 (12).

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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. © 2024 The Author(s)

Item Type:	Journal Article
Publication:	iScience
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to the publishers.
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	23 Dec 2024 08:42
Last Modified:	23 Dec 2024 08:42
URI:	http://eprints.iisc.ac.in/id/eprint/87121

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