{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:48:43Z","timestamp":1791946123673,"version":"4.3.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T00:00:00Z","timestamp":1650067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Medical Centre Utrecht"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2212\/\u2212 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiac114","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T03:58:28Z","timestamp":1649995108000},"page":"258-269","source":"Crossref","is-referenced-by-count":16,"title":["Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient"],"prefix":"10.1093","volume":"226","author":[{"given":"Sjanna B","family":"Besteman","sequence":"first","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"},{"name":"Department of Pediatrics, Wilhelmina Children\u2019s Hospital, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Phung","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette H M","family":"Raeven","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gimano D","family":"Amatngalim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matev\u017e","family":"Rumpret","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"},{"name":"Oncode Institute , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Crabtree","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutger M","family":"Schepp","sequence":"additional","affiliation":[{"name":"National Institute of Public Health and the Environment (RIVM) , Bilthoven , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa W","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna G","family":"Siemonsma","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nile","family":"Verleur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wilhelmina Children\u2019s Hospital, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne","family":"van Slooten","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs W","family":"van Haaften","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Beekman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"},{"name":"Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht University , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A","family":"Chang","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linde","family":"Meyaard","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"},{"name":"Oncode Institute , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjomme","family":"van der Bruggen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Medical Center Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A M","family":"Berbers","sequence":"additional","affiliation":[{"name":"National Institute of Public Health and the Environment (RIVM) , Bilthoven , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Derksen","sequence":"additional","affiliation":[{"name":"RSV Patient Network, ReSVinet , Zeist , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nierkens","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn M","family":"Morabito","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy J","family":"Ruckwardt","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious 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