Journal Article

CX3CR1 Is Expressed in Differentiated Human Ciliated Airway Cells and Co-Localizes with Respiratory Syncytial Virus on Cilia in a G Protein-Dependent Manner

Parrington, Mark, Kishko, Michael, Groppo, Rachel P., Zhang, Linong, Jeong, Kwang-Il, DiNapoli, Joshua M., Kleanthous, Harry, Almond, Jeffrey, Delagrave, Simon, Piepenhagen, Peter A.

2015

Overview

Respiratory syncytial virus (RSV) is the principal cause of bronchiolitis in infants and a significant healthcare problem. The RSV Glycoprotein (G) mediates attachment of the virus to the cell membrane, which facilitates interaction of the RSV Fusion (F) protein with nucleolin, thereby triggering fusion of the viral and cellular membranes. However, a host protein ligand for G has not yet been identified. Here we show that CX3CR1 is expressed in the motile cilia of differentiated human airway epithelial (HAE) cells, and that CX3CR1 co-localizes with RSV particles. Upon infection, the distribution of CX3CR1 in these cells is significantly altered. Complete or partial deletion of RSV G results in viruses binding at least 72-fold less efficiently to cells, and reduces virus replication. Moreover, an antibody targeting an epitope near the G protein's CX3CR1-binding motif significantly inhibits binding of the virus to airway cells. Given previously published evidence of the interaction of G with CX3CR1 in human lymphocytes, these findings suggest a role for G in the interaction of RSV with ciliated lung cells. This interpretation is consistent with past studies showing a protective benefit in immunizing against G in animal models of RSV infection, and would support targeting the CX3CR1-G protein interaction for prophylaxis or therapy. CX3CR1 expression in lung epithelial cells may also have implications for other respiratory diseases such as asthma.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Antibodies - pharmacology / Asthma / Base Sequence / Binding / Binding Sites / Bronchopneumonia / Cell culture / Cell Differentiation / Chemokines / Child / Cilia / Cilia - metabolism / Cilia - pathology / Cilia - virology / Clonal deletion / CX3C Chemokine Receptor 1 / CX3CR1 protein / Disease prevention / Epithelial cells / Epithelial Cells - metabolism / Epithelial Cells - pathology / Epithelial Cells - virology / Epitopes / Epitopes - chemistry / Epitopes - immunology / Fusion protein / G proteins / Gene Expression / Glycoproteins / Health aspects / Health care / Heparan sulfate / Humans / Immunization / Immunoglobulins / Infants / Infection / Infections / Lungs / Lymphocytes / Membranes / Microscopy / Molecular Sequence Data / Nucleolin / Primary Cell Culture / Prophylaxis / Protein Binding / Proteins / Receptors, Chemokine - antagonists & inhibitors / Receptors, Chemokine - chemistry / Receptors, Chemokine - genetics / Receptors, Chemokine - metabolism / Respiratory diseases / Respiratory Mucosa - metabolism / Respiratory Mucosa - pathology / Respiratory Mucosa - virology / Respiratory syncytial virus / Respiratory Syncytial Virus, Human - genetics / Respiratory Syncytial Virus, Human - metabolism / Respiratory tract / Sequence Deletion / Viral Envelope Proteins - antagonists & inhibitors / Viral Envelope Proteins - chemistry / Viral Envelope Proteins - genetics / Viral Envelope Proteins - metabolism / Viral Fusion Proteins - chemistry / Viral Fusion Proteins - genetics / Viral Fusion Proteins - metabolism / Virology / Viruses