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 (3CLpro) encoded by diverse coronaviruses, including Severe Acute Respiratory S...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002144 |
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| author | Brian V Tsu Rimjhim Agarwal Nandan S Gokhale Jessie Kulsuptrakul Andrew P Ryan Elizabeth J Fay Lennice K Castro Christopher Beierschmitt Christina Yap Elizabeth A Turcotte Sofia E Delgado-Rodriguez Russell E Vance Jennifer L Hyde Ram Savan Patrick S Mitchell Matthew D Daugherty |
| author_facet | Brian V Tsu Rimjhim Agarwal Nandan S Gokhale Jessie Kulsuptrakul Andrew P Ryan Elizabeth J Fay Lennice K Castro Christopher Beierschmitt Christina Yap Elizabeth A Turcotte Sofia E Delgado-Rodriguez Russell E Vance Jennifer L Hyde Ram Savan Patrick S Mitchell Matthew D Daugherty |
| author_sort | Brian V Tsu |
| collection | DOAJ |
| description | 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 (3CLpro) 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 3CLpro, including 3CLpro-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 3CLpros and, instead, enables sensing of 3C proteases (3Cpro) 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. |
| format | Article |
| id | doaj-art-cdf5043f3dfb4817b3329b51ef3b0db4 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-cdf5043f3dfb4817b3329b51ef3b0db42025-08-20T02:38:31ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-06-01216e300214410.1371/journal.pbio.3002144Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome.Brian V TsuRimjhim AgarwalNandan S GokhaleJessie KulsuptrakulAndrew P RyanElizabeth J FayLennice K CastroChristopher BeierschmittChristina YapElizabeth A TurcotteSofia E Delgado-RodriguezRussell E VanceJennifer L HydeRam SavanPatrick S MitchellMatthew D DaughertyHosts 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 (3CLpro) 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 3CLpro, including 3CLpro-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 3CLpros and, instead, enables sensing of 3C proteases (3Cpro) 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.https://doi.org/10.1371/journal.pbio.3002144 |
| spellingShingle | Brian V Tsu Rimjhim Agarwal Nandan S Gokhale Jessie Kulsuptrakul Andrew P Ryan Elizabeth J Fay Lennice K Castro Christopher Beierschmitt Christina Yap Elizabeth A Turcotte Sofia E Delgado-Rodriguez Russell E Vance Jennifer L Hyde Ram Savan Patrick S Mitchell Matthew D Daugherty Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. PLoS Biology |
| title | Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. |
| title_full | Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. |
| title_fullStr | Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. |
| title_full_unstemmed | Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. |
| title_short | Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. |
| title_sort | host specific sensing of coronaviruses and picornaviruses by the card8 inflammasome |
| url | https://doi.org/10.1371/journal.pbio.3002144 |
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