{"doi":"10.1172/jci162694","title":"Human NK cells confer protection against HIV-1 infection in humanized mice","abstract":"The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound after analytic treatment interruption. Moreover, a broadly neutralizing antibody, PGT121, enhanced NK cell function in vivo, consistent with antibody-dependent cellular cytotoxicity. Monoclonal antibody depletion of NK cells resulted in higher viral loads in multiple nonlymphoid organs. Overall, our results in humanized MISTRG-6-15 mice demonstrated that NK cells provided direct anti-HIV-1 responses in vivo but were limited in their responses in lymphoid organs.","journal":"Journal of Clinical Investigation","year":2022,"id":243418,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":576119,"name":"Qiankun Wang","orcid":"0000-0003-3508-960X","position":1,"is_corresponding":false},{"id":565913,"name":"Ayşe Naz Ozantürk","orcid":"0000-0002-0187-3642","position":2,"is_corresponding":false},{"id":367518,"name":"Hongbo Gao","orcid":"0009-0002-2992-3960","position":3,"is_corresponding":false},{"id":225533,"name":"Aaron J. Schmitz","orcid":"0000-0002-8077-6751","position":4,"is_corresponding":false},{"id":109978,"name":"Marina Cella","orcid":"0000-0003-1230-1313","position":5,"is_corresponding":false},{"id":276885,"name":"Wayne M. Yokoyama","orcid":"0000-0002-0566-7264","position":6,"is_corresponding":false},{"id":413853,"name":"Liang Shan","orcid":"0000-0002-8833-2514","position":7,"is_corresponding":false},{"id":875231,"name":"Can M. Sungur","orcid":"0000-0002-6937-8525","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"36282589","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":[]}