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Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome

Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CL(pro)) encoded by diverse coronaviruses, including Severe Acute Respiratory...

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Detalles Bibliográficos
Autores principales: Tsu, Brian V., Agarwal, Rimjhim, Gokhale, Nandan S., Kulsuptrakul, Jessie, Ryan, Andrew P., Fay, Elizabeth J., Castro, Lennice K., Beierschmitt, Christopher, Yap, Christina, Turcotte, Elizabeth A., Delgado-Rodriguez, Sofia E., Vance, Russell E., Hyde, Jennifer L., Savan, Ram, Mitchell, Patrick S., Daugherty, Matthew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249858/
https://www.ncbi.nlm.nih.gov/pubmed/37289745
http://dx.doi.org/10.1371/journal.pbio.3002144
Descripción
Sumario:Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CL(pro)) encoded by diverse coronaviruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), cleaves a rapidly evolving region of human CARD8 and activates a robust inflammasome response. CARD8 is required for cell death and the release of pro-inflammatory cytokines during SARS-CoV-2 infection. We further find that natural variation alters CARD8 sensing of 3CL(pro), including 3CL(pro)-mediated antagonism rather than activation of megabat CARD8. Likewise, we find that a single nucleotide polymorphism (SNP) in humans reduces CARD8’s ability to sense coronavirus 3CL(pros) and, instead, enables sensing of 3C proteases (3C(pro)) from select picornaviruses. Our findings demonstrate that CARD8 is a broad sensor of viral protease activities and suggests that CARD8 diversity contributes to inter- and intraspecies variation in inflammasome-mediated viral sensing and immunopathology.