Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient. (16th April 2022)

• Record Type: Journal Article
• Authors: Besteman, Sjanna B; Phung, Emily; Raeven, Henriette H M; Amatngalim, Gimano D; Rumpret, Matevž; Crabtree, Juliet; Schepp, Rutger M; Rodenburg, Lisa W; Siemonsma, Susanna G; Verleur, Nile; van Slooten, Rianne; Duran, Karen; van Haaften, Gijs W; Beekman, Jeffrey M; Chang, Lauren A; Meyaard, Linde; van der Bruggen, Tjomme; Berbers, Guy A M; Derksen, Nicole; Nierkens, Stefan; Morabito, Kaitlyn M; Ruckwardt, Tracy J; Kurt-Jones, Evelyn A; Golenbock, Douglas; Graham, Barney S; Bont, Louis J
• Is Part Of: Journal of infectious diseases. Volume 226:Number 2(2022)
• Page Start: 258
• Page End: 269
• Publication Date: 2022-04-16
• Subjects: CD14 -- epithelium -- monocyte -- respiratory syncytial virus -- Toll-like receptor; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac114
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : Autosomal recessive CD14 deficiency is a novel genetic etiology associated with recurrent RSV bronchiolitis. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein.