{"doi":"10.3390/v17081099","title":"Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART","abstract":"Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity. Furthermore, IFNAR blockade rescues ILC3 functionality, which is critical for IL-17/IL-22-mediated antimicrobial defense and mucosal barrier maintenance. Our study delineates IFN-I-driven immunosuppression across innate lymphocyte compartments and proposes the targeted modulation of this pathway to enhance antiviral and mucosal immunity in HIV-1 management.","journal":"Viruses","year":2025,"id":553816,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398077,"name":"Haisheng Yu","orcid":"0000-0002-1757-1411","position":1,"is_corresponding":false},{"id":603607,"name":"Guangming Li","orcid":"0000-0003-2925-3792","position":2,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":3,"is_corresponding":false},{"id":537938,"name":"Liang Cheng","orcid":"0000-0001-6049-5293","position":4,"is_corresponding":false},{"id":1450738,"name":"R.J. Han","orcid":"0000-0002-4646-6928","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40872811","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":[]}