{"doi":"10.1016/j.celrep.2021.109735","title":"An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins","abstract":"Subtype C is the most prevalent clade of human immunodeficiency virus type 1 (HIV-1) worldwide. The reasons for this are poorly understood. Here, we demonstrate that a characteristic additional third nuclear factor κB (NF-κB) binding site in the long terminal repeat (LTR) promoter allows subtype C HIV-1 strains to evade restriction by nuclear PYHIN proteins, which sequester the transcription factor Sp1. Further, other LTR alterations are responsible for rare PYHIN resistance of subtype B viruses. Resistance-conferring mutations generally reduce the dependency of HIV-1 on Sp1 for virus production and render LTR transcription highly responsive to stimulation by NF-κB/p65. A third NF-κB binding site increases infectious virus yield in primary CD4 + T cells in an γ-interferon-inducible protein 16 (IFI16)-dependent manner. Comprehensive sequence analyses suggest that the frequency of circulating PYHIN-resistant HIV-1 strains is increasing. Our finding that an additional NF-κB binding site in the LTR confers resistance to nuclear PYHIN proteins helps to explain the dominance of clade C HIV-1 strains.","journal":"Cell Reports","year":2021,"id":182946,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":386592,"name":"Christina M. Stürzel","orcid":null,"position":1,"is_corresponding":false},{"id":576033,"name":"Dorota Kmieć","orcid":"0000-0001-7302-6015","position":2,"is_corresponding":false},{"id":735954,"name":"Smitha Srinivasachar Badarinarayan","orcid":"0000-0002-4591-0513","position":3,"is_corresponding":false},{"id":736645,"name":"Elisabeth Braun","orcid":null,"position":4,"is_corresponding":false},{"id":258983,"name":"Jumpei Ito","orcid":"0000-0003-0440-8321","position":5,"is_corresponding":false},{"id":37911,"name":"Kei Sato","orcid":"0000-0003-4431-1380","position":6,"is_corresponding":false},{"id":91120,"name":"Beatrice H. Hahn","orcid":"0000-0002-9400-9887","position":7,"is_corresponding":false},{"id":468046,"name":"Konstantin M. J. Sparrer","orcid":"0000-0002-8682-1779","position":8,"is_corresponding":false},{"id":381612,"name":"Daniel Sauter","orcid":"0000-0001-7665-0040","position":9,"is_corresponding":false},{"id":350334,"name":"Frank Kirchhoff","orcid":"0000-0002-7052-2360","position":10,"is_corresponding":false},{"id":468036,"name":"Matteo Bosso","orcid":"0000-0001-9344-9963","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:48:17.816498Z","pmid":"34551301","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":[]}