{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hughes IK"],"funding":["NIDA NIH HHS","NIAID NIH HHS"],"pagination":["eadz1069"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12609157"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(46)"],"pubmed_abstract":["As intracellular parasites, viruses must devise sophisticated mechanisms to produce and assemble viral components while suppressing activation of innate immune effectors. Here, we report that coordination of HIV-1 assembly by the viral polyprotein Gag suppresses inappropriately timed protease (PR) activity to evade the PR activity sensor, caspase recruitment domain-containing protein 8 (CARD8). Using mutants of Gag, we show that disruption of domains controlling viral assembly site [matrix (MA)] or virus particle release (nucleocapsid and p6) leads to premature activation of PR and the CARD8 inflammasome, resulting in interleukin-1β (IL-1β) secretion and pyroptotic cell death. Further, we demonstrate that previously observed host-adaptive mutations in HIV-1 MA (M30K) and p6 (PTAP duplicati"],"journal":["Science advances"],"pubmed_title":["Evasion of CARD8 activation during HIV-1 assembly."],"pmcid":["PMC12609157"],"funding_grant_id":["R01 AI187175","R01 DA051889","R01 DA059952","P30 AI042853","R01 DA055488"],"pubmed_authors":["Hughes IK","Akiyama H","Hood JB","Gummuluru S","Quinones-Molina AA"],"additional_accession":[]},"is_claimable":false,"name":"Evasion of CARD8 activation during HIV-1 assembly.","description":"As intracellular parasites, viruses must devise sophisticated mechanisms to produce and assemble viral components while suppressing activation of innate immune effectors. Here, we report that coordination of HIV-1 assembly by the viral polyprotein Gag suppresses inappropriately timed protease (PR) activity to evade the PR activity sensor, caspase recruitment domain-containing protein 8 (CARD8). Using mutants of Gag, we show that disruption of domains controlling viral assembly site [matrix (MA)] or virus particle release (nucleocapsid and p6) leads to premature activation of PR and the CARD8 inflammasome, resulting in interleukin-1β (IL-1β) secretion and pyroptotic cell death. Further, we demonstrate that previously observed host-adaptive mutations in HIV-1 MA (M30K) and p6 (PTAP duplicati","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T16:14:14.89Z","creation":"2026-05-18T03:12:51.476Z"},"accession":"S-EPMC12609157","cross_references":{"pubmed":["41223282"],"doi":["10.1126/sciadv.adz1069"]}}