Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures.
Sara M. Johnson,Sara M. Johnson,Beth A. McNally,Beth A. McNally,Ioannis Ioannidis,Ioannis Ioannidis,Emilio Flaño,Emilio Flaño,Michael N. Teng,Antonius G. P. Oomens,Edward E. Walsh,Mark E. Peeples,Mark E. Peeples +12 more
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TLDR
It is demonstrated that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.Abstract:
Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE) cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a “non-neutralizing” monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.read more
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Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment
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Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?
TL;DR: The current knowledge on HSPG–virus interactions is summarized and viruses with established HS binding, viruses that bind HS only after intra-host or cell culture adaptation, and finally, viruses whose dependence on HS for infection is debated are distinguished.
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Journal ArticleDOI
Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis
Harish Nair,Harish Nair,D. James Nokes,D. James Nokes,Bradford D. Gessner,Mukesh Dherani,Shabir A. Madhi,Rosalyn J. Singleton,Katherine L. O'Brien,Anna Roca,Anna Roca,Peter F. Wright,Nigel Bruce,Aruna Chandran,Evropi Theodoratou,Agustinus Sutanto,Endang R. Sedyaningsih,Mwanajuma Ngama,Patrick K. Munywoki,Cissy B. Kartasasmita,Eric A. F. Simões,Igor Rudan,Igor Rudan,Martin Weber,Harry Campbell +24 more
TL;DR: Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b, and the development of novel prevention and treatment strategies should be accelerated as a priority.
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Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion.
Steffen Jung,Julio Aliberti,Petra Graemmel,Mary Jean Sunshine,Georg W. Kreutzberg,Alan Sher,Dan R. Littman +6 more
TL;DR: Defying anticipated FKN functions, absence of CX3CR1 interferes neither with monocyte extravasation in a peritonitis model nor with DC migration and differentiation in response to microbial antigens or contact sensitizers.
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Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion
Toshio Imai,Kunio Hieshima,Christopher Haskell,Masataka Baba,Morio Nagira,Miyuki Nishimura,Mayumi Kakizaki,Shin Takagi,Hisayuki Nomiyama,Thomas J. Schall,Osamu Yoshie +10 more
TL;DR: Fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions.
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David K. Shay,Robert C. Holman,Robert D. Newman,Lenna L. Liu,James W. Stout,Larry J. Anderson +5 more
TL;DR: Rates of bronchiolitis-associated hospitalizations associated with RSV infection among infants may be greater than previous estimates for RSV bron chiolitis and pneumonia hospitalizations combined.
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