{"doi":"10.1093/infdis/jiac114","title":"Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient","abstract":"BACKGROUND: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection. METHODS: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection. RESULTS: Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14-/- HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production. CONCLUSIONS: We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication.","journal":"The Journal of Infectious Diseases","year":2022,"id":259716,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105590,"name":"Emily Phung","orcid":"0000-0001-9684-9698","position":1,"is_corresponding":false},{"id":912849,"name":"Henriette H. 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Rodenburg","orcid":"0000-0002-8113-4304","position":7,"is_corresponding":false},{"id":912850,"name":"Susanna G Siemonsma","orcid":null,"position":8,"is_corresponding":false},{"id":912851,"name":"Nile Verleur","orcid":null,"position":9,"is_corresponding":false},{"id":912852,"name":"Rianne van Slooten","orcid":null,"position":10,"is_corresponding":false},{"id":912853,"name":"Karen Duran","orcid":null,"position":11,"is_corresponding":false},{"id":912854,"name":"Gijs W. van Haaften","orcid":null,"position":12,"is_corresponding":false},{"id":879792,"name":"Jeffrey M. Beekman","orcid":"0000-0003-4886-3756","position":13,"is_corresponding":false},{"id":105591,"name":"Lauren A. 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