{"doi":"10.17615/cc74-by90","title":"Humanized mice engrafted with human HSC only or HSC and thymus support comparable HIV-1 replication, immunopathology, and responses to ART and immune therapy","abstract":"Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2-/-/γc-/- (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors. We found that similar human lymphoid and myeloid lineages were reconstituted in NRG-hu HSC and NRG-hu Thy/HSC mice, with human T cells more predominantly reconstituted in NRG-hu Thy/HSC mice, while NRG-hu HSC mice supported more human B cells and myeloid cells reconstitution. HIV-1 replicated similarly and induced similar T cell depletion, immune activation, and dysfunction in NRG-hu HSC and NRG-hu Thy/HSC mice. Moreover, combined antiretroviral therapy (cART) inhibited HIV-1 replication efficiently with similar persistent HIV-1 reservoirs in both models. Finally, we found that blocking type-I interferon signaling under cART treatment transiently activated HIV-1 reservoirs, enhanced T cell recovery and reduced HIV-1 reservoirs in both HIV-1 infected NRG-hu HSC and NRG-hu Thy/HSC mice. In summary, we report that NRG-hu Thy/HSC and NRG-hu HSC mice support similar HIV-1 infection and similar HIV-1 immunopathology; and HIV-1 replication responds similarly to cART and IFNAR blockade therapies. The NRG-hu HSC mouse model reconstituted with human HSC only is sufficient for the study of HIV-1 infection, pathogenesis, and therapy.","journal":"UNC Libraries","year":2020,"id":140044,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8446,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":1,"is_corresponding":false},{"id":604276,"name":"Jinping Ma","orcid":null,"position":2,"is_corresponding":false},{"id":537938,"name":"Liang Cheng","orcid":"0000-0001-6049-5293","position":3,"is_corresponding":false},{"id":603607,"name":"Guangming Li","orcid":"0000-0003-2925-3792","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:13.583586Z","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":[]}