{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:26:13Z","timestamp":1789050373774,"version":"build-2803163510"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"46","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,11,14]]},"abstract":"<jats:p>\n                    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-1\u03b2 (IL-1\u03b2) secretion and pyroptotic cell death. Further, we demonstrate that previously observed host-adaptive mutations in HIV-1 MA (M30K) and p6 (PTAP duplication) associated with greater fitness in humans improve infected CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell survival in a PR-dependent manner, which may be regulated by CARD8. Together, this work reveals virus-encoded mechanistic control over PR activation and CARD8 sensing by HIV-1 Gag.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz1069","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T18:58:51Z","timestamp":1762973931000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Evasion of CARD8 activation during HIV-1 assembly"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8769-4011","authenticated-orcid":true,"given":"Ivy K.","family":"Hughes","sequence":"first","affiliation":[{"name":"Department of Virology, Immunology, &amp; Microbiology, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA 02118, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3354-7787","authenticated-orcid":true,"given":"James 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