{"doi":"10.17615/qchm-zf12","title":"Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs","abstract":"Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1–infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1–induced immune hyperactivation and rescued anti–HIV-1 immune responses in T cells from HIV-1–infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1–infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1–associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.","journal":"UNC Libraries","year":2020,"id":137778,"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":0.9581,"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":599051,"name":"Fumihiko Yasui","orcid":null,"position":1,"is_corresponding":false},{"id":599052,"name":"Chaobaihui Ye","orcid":null,"position":2,"is_corresponding":false},{"id":599053,"name":"Jianping Ma","orcid":null,"position":3,"is_corresponding":false},{"id":598444,"name":"Dan Li","orcid":"0000-0001-7351-5548","position":4,"is_corresponding":false},{"id":398077,"name":"Haisheng Yu","orcid":"0000-0002-1757-1411","position":5,"is_corresponding":false},{"id":292618,"name":"Feng Li","orcid":"0000-0002-8904-2893","position":6,"is_corresponding":false},{"id":398078,"name":"Guangming Li","orcid":"0000-0002-0281-8258","position":7,"is_corresponding":false},{"id":327189,"name":"Qing Zhang","orcid":"0000-0002-6595-8995","position":8,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":9,"is_corresponding":false},{"id":480682,"name":"Li-Chung Tsao","orcid":"0000-0003-2136-0585","position":10,"is_corresponding":false},{"id":16291,"name":"Liang Cheng","orcid":"0000-0002-6665-6710","position":11,"is_corresponding":false},{"id":398080,"name":"Zhiyuan Hu","orcid":"0000-0002-2963-2453","position":12,"is_corresponding":false},{"id":531569,"name":"Liguo Zhang","orcid":"0000-0002-9795-0314","position":13,"is_corresponding":false},{"id":598443,"name":"Jingyun Li","orcid":"0000-0003-1321-2582","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","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":[]}