{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Parameswaran P"],"funding":["Richard and Susan Smith Family Foundation","UMass Chan Medical School","NIAID NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["e20231518"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11167375"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(8)"],"pubmed_abstract":["Guard proteins initiate defense mechanisms upon sensing pathogen-encoded virulence factors. Successful viral pathogens likely inhibit guard protein activity, but these interactions have been largely undefined. Here, we demonstrate that the human pathogen herpes simplex virus 1 (HSV-1) stimulates and inhibits an antiviral pathway initiated by NLRP1, a guard protein that induces inflammasome formation and pyroptotic cell death when activated. Notably, HSV-1 infection of human keratinocytes promotes posttranslational modifications to NLRP1, consistent with MAPK-dependent NLRP1 activation, but does not result in downstream inflammasome formation. We identify infected cell protein 0 (ICP0) as the critical HSV-1 protein that is necessary and sufficient for inhibition of the NLRP1 pathway. Mechan"],"journal":["The Journal of experimental medicine"],"pubmed_title":["A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome."],"pmcid":["PMC11167375"],"funding_grant_id":["R00AI130258","R00 AI130258"],"pubmed_authors":["Orzalli MH","Parameswaran P","Rashighi M","Payne L","Powers J"],"additional_accession":[]},"is_claimable":false,"name":"A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.","description":"Guard proteins initiate defense mechanisms upon sensing pathogen-encoded virulence factors. Successful viral pathogens likely inhibit guard protein activity, but these interactions have been largely undefined. Here, we demonstrate that the human pathogen herpes simplex virus 1 (HSV-1) stimulates and inhibits an antiviral pathway initiated by NLRP1, a guard protein that induces inflammasome formation and pyroptotic cell death when activated. Notably, HSV-1 infection of human keratinocytes promotes posttranslational modifications to NLRP1, consistent with MAPK-dependent NLRP1 activation, but does not result in downstream inflammasome formation. We identify infected cell protein 0 (ICP0) as the critical HSV-1 protein that is necessary and sufficient for inhibition of the NLRP1 pathway. Mechan","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-02T04:38:57.111Z","creation":"2025-04-19T14:38:13.192Z"},"accession":"S-EPMC11167375","cross_references":{"pubmed":["38861480"],"doi":["10.1084/jem.20231518"]}}