CX3CR1 is an Important Surface Molecule for RSV Infection in Human Airway Epithelial Cells.
AUTHORS
- PMID: 26297201 [PubMed].
ABSTRACT
Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and bronchiolitis in infants and young children and causes disease throughout life. Understanding biology of infection, including virus binding to the cell surface, should help develop anti-viral drugs or vaccines. The RSV F and G glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through heparin binding domains. G also has a CX3C chemokine motif which binds to the fractalkine receptor CX3CR1. G binding to CX3CR1 is not important to infection of immortalized cell lines but reportedly is so for primary human airway epithelial cells (HAECs), the primary site for human infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines, HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif. Immortalized cells lacking HSPGs had low RSV binding and infection, which was markedly increased by CX3CR1 transfection. CX3CR1 was expressed primarily on ciliated cells, and approximately 50% of RSV-infected cells in HAECs were CX3CR1 positive. HAECs with more CX3CR1-expressing cells had a proportional increase in RSV infection. Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C motif significantly decreased RSV infection in HAECs. The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES, IL-8, and fractalkine production while down-regulated IL-15, IL1-RA and MCP-1. Thus, the RSV G protein CX3C/CX3CR1 interaction is likely important in infection and infection-induced responses of airway epithelium, the primary site for human infection.
Respiratory syncytial virus (RSV) is a major cause of severe pneumonia and bronchiolitis in infants and young children and causes disease throughout life. Understanding biology of infection, including virus binding to the cell surface, should help develop anti-viral drugs or vaccines. The RSV F and G glycoproteins bind cell surface heparin sulfate proteoglycans (HSPGs) through heparin binding domains. G also has a CX3C chemokine motif which binds to the fractalkine receptor CX3CR1. G binding to CX3CR1 is not important to infection of immortalized cell lines but reportedly is so for primary human airway epithelial cells (HAECs), the primary site for human infection. We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines, HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif. Immortalized cells lacking HSPGs had low RSV binding and infection, which was markedly increased by CX3CR1 transfection. CX3CR1 was expressed primarily on ciliated cells, and approximately 50% of RSV-infected cells in HAECs were CX3CR1 positive. HAECs with more CX3CR1-expressing cells had a proportional increase in RSV infection. Blocking G binding to CX3CR1 with anti-CX3CR1 antibody or a mutation in the CX3C motif significantly decreased RSV infection in HAECs. The kinetics of cytokine production suggested that the RSV/CX3CR1 interaction induced RANTES, IL-8, and fractalkine production while down-regulated IL-15, IL1-RA and MCP-1. Thus, the RSV G protein CX3C/CX3CR1 interaction is likely important in infection and infection-induced responses of airway epithelium, the primary site for human infection.
Tags: Alumni Publications 2015