{"doi":"10.1101/2023.03.18.533283","title":"The CARD8 inflammasome drives CD4 <sup>+</sup> T-cell depletion in HIV-1 infection","abstract":"Abstract CD4 + T-cell depletion is the root cause of acquired immunodeficiency syndrome (AIDS). How HIV depletes CD4 + T cells in humans remains unknown because vast majority of the dying CD4 + T cells in patients are uninfected. Burgeoning evidence supports the hypothesis that non-productive HIV-1 infection triggers CD4 + T-cell depletion in the course of pathogenic HIV and SIV infections. Here, we report that the CARD8 inflammasome is activated immediately after HIV-1 entry by the viral protease encapsulated in the incoming HIV-1 particles. Sensing of HIV-1 protease activity by the CARD8 inflammasome leads to rapid pyroptosis of quiescent CD4 + T cells without productive viral infection. In humanized mice reconstituted with a CARD8-deficient immune system, CD4 + T-cell loss is delayed despite increased levels of HIV-1 replication. Our study suggests that the CARD8 inflammasome drives CD4 + T-cell depletion and disease progression through rapid sensing of HIV-1 particles.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398806,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":413853,"name":"Liang Shan","orcid":"0000-0002-8833-2514","position":1,"is_corresponding":false},{"id":576119,"name":"Qiankun Wang","orcid":"0000-0003-3508-960X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:47.744358Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}