Recurrent Respiratory Syncytial Virus Infection in a CD14-Deficient Patient

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2022 Apr 16

PMID 35429403

Authors

Sjanna B Besteman

Emily Phung

Henriette H M Raeven

Gimano D Amatngalim

Matevz Rumpret

Juliet Crabtree

Rutger M Schepp

Lisa W Rodenburg

Susanna G Siemonsma

Nile Verleur

Rianne van Slooten

Karen Duran

Gijs W van Haaften

Jeffrey M Beekman

Lauren A Chang

Linde Meyaard

Tjomme van der Bruggen

Guy A M Berbers

Nicole Derksen

Stefan Nierkens

Kaitlyn M Morabito

Tracy J Ruckwardt

Evelyn A Kurt-Jones

Douglas Golenbock

Barney S Graham

Louis J Bont

Affiliations

Soon will be listed here.

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.

Citing Articles

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