{"doi":"10.3390/v15020365","title":"Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection","abstract":"Mice reconstituted with human immune systems are instrumental in the investigation of HIV-1 pathogenesis and therapeutics. Natural killer (NK) cells have long been recognized as a key mediator of innate anti-HIV responses. However, established humanized mouse models do not support robust human NK cell development from engrafted human hematopoietic stem cells (HSCs). A major obstacle to human NK cell reconstitution is the lack of human interleukin-15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor. Here, we demonstrate that immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice expressing a transgene encoding human IL-15 (NSG-Tg(IL-15)) have physiological levels of human IL-15 and support long-term engraftment of human NK cells when transplanted with human umbilical-cord-blood-derived HSCs. These Hu-NSG-Tg(IL-15) mice demonstrate robust and long-term reconstitution with human immune cells, but do not develop graft-versus-host disease (GVHD), allowing for long-term studies of human NK cells. Finally, we show that these HSC engrafted mice can sustain HIV-1 infection, resulting in human NK cell responses in HIV-infected mice. We conclude that Hu-NSG-Tg(IL-15) mice are a robust novel model to study NK cell responses to HIV-1.","journal":"Viruses","year":2023,"id":331612,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":724181,"name":"Tridu R. Huynh","orcid":"0000-0002-7945-2792","position":1,"is_corresponding":false},{"id":368832,"name":"Abeera Mehmood","orcid":"0000-0002-3850-1551","position":2,"is_corresponding":false},{"id":1056950,"name":"Teha Kim","orcid":"0000-0002-4421-4620","position":3,"is_corresponding":false},{"id":287983,"name":"Kayla Frank","orcid":"0000-0002-8150-6657","position":4,"is_corresponding":false},{"id":1056951,"name":"Kefei Gao","orcid":"0009-0008-0291-4101","position":5,"is_corresponding":false},{"id":724182,"name":"Cristina Zalfa","orcid":"0000-0001-8472-1961","position":6,"is_corresponding":false},{"id":1057634,"name":"Angel Gandarilla","orcid":null,"position":7,"is_corresponding":false},{"id":239998,"name":"Leonard D. Shultz","orcid":"0000-0002-4868-1031","position":8,"is_corresponding":false},{"id":267158,"name":"Silke Paust","orcid":"0000-0002-0526-3999","position":9,"is_corresponding":false},{"id":703742,"name":"Shawn Abeynaike","orcid":"0000-0002-0346-624X","position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-19T01:09:25.015646Z","pmid":"36851579","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":[]}