{"doi":"10.1089/aid.2023.0114","title":"Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1","abstract":"Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.","journal":"AIDS Research and Human Retroviruses","year":2024,"id":466002,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":412274,"name":"Esther Lee","orcid":"0000-0003-1149-6331","position":1,"is_corresponding":false},{"id":1149514,"name":"Melissa Craemer","orcid":null,"position":2,"is_corresponding":false},{"id":1298260,"name":"Alayna Pruitt","orcid":null,"position":3,"is_corresponding":false},{"id":831429,"name":"Harikrishnan Balachandran","orcid":"0000-0001-9336-0555","position":4,"is_corresponding":false},{"id":1149031,"name":"Simon B. Gressens","orcid":"0000-0002-4993-6956","position":5,"is_corresponding":false},{"id":435422,"name":"Kyle Kroll","orcid":"0000-0002-9237-9497","position":6,"is_corresponding":false},{"id":436692,"name":"Cordelia Manickam","orcid":null,"position":7,"is_corresponding":false},{"id":449696,"name":"Yuxing Li","orcid":"0000-0001-9785-2960","position":8,"is_corresponding":false},{"id":778384,"name":"Stéphanie Jost","orcid":"0000-0003-2100-3262","position":9,"is_corresponding":false},{"id":765188,"name":"Griffin Woolley","orcid":null,"position":10,"is_corresponding":false},{"id":107632,"name":"R. Keith Reeves","orcid":"0000-0003-3157-2557","position":11,"is_corresponding":false},{"id":494501,"name":"Sho K. Sugawara","orcid":"0000-0002-5187-423X","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:04:54.606394Z","pmid":"39041622","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":[]}