{"doi":"10.17615/fy9f-bc07","title":"Restriction of HIV-1 infection in sickle cell trait","abstract":"Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women InteragencyHIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.","journal":"UNC Libraries","year":2023,"id":415870,"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":0.9656,"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":591317,"name":"K. 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Fischl","orcid":null,"position":11,"is_corresponding":false},{"id":251683,"name":"M. Neale Weitzmann","orcid":"0000-0003-3305-5748","position":12,"is_corresponding":false},{"id":1198276,"name":"A.L. French","orcid":null,"position":13,"is_corresponding":false},{"id":596997,"name":"S. Kassaye","orcid":null,"position":14,"is_corresponding":false},{"id":1197948,"name":"Asmala Ahmad","orcid":"0000-0001-6180-1678","position":15,"is_corresponding":false},{"id":570107,"name":"Namita Kumari","orcid":"0000-0003-0893-9939","position":16,"is_corresponding":false},{"id":596996,"name":"S. Gange","orcid":null,"position":17,"is_corresponding":false},{"id":1198249,"name":"J. Lazar","orcid":null,"position":18,"is_corresponding":false},{"id":529423,"name":"D.F. Nixon","orcid":null,"position":19,"is_corresponding":false},{"id":295824,"name":"Miguel de Mulder Rougvie","orcid":"0000-0002-8026-7076","position":20,"is_corresponding":false},{"id":1198319,"name":"Patricia E. 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