Abstract
Background
Data on the host factors that contribute to infection of young children by respiratory syncytial virus (RSV) are limited. The human chemokine receptor, CX3CR1, has recently been implicated as an RSV receptor. Here we evaluate a role for CX3CR1 in pediatric lung RSV infections.
Methods
CX3CR1 transcript levels in the upper and lower pediatric airways were assessed. Tissue localization and cell-specific expression was confirmed using in situ hybridization and immunohistochemistry. The role of CX3CR1 in RSV infection was also investigated using a novel physiological model of pediatric epithelial cells.
Results
Low levels of CX3CR1 transcript were often, but not always, expressed in both upper (62%) and lower airways (36%) of pediatric subjects. CX3CR1 transcript and protein expression was detected in epithelial cells of normal human pediatric lung tissues. CX3CR1 expression was readily detected on primary cultures of differentiated pediatric/infant human lung epithelial cells. RSV demonstrated preferential infection of CX3CR1-positive cells, and blocking CX3CR1/RSV interaction significantly decreased viral load.
Conclusion
CX3CR1 is present in the airways of pediatric subjects where it may serve as a receptor for RSV infection. Furthermore, CX3CR1 appears to play a mechanistic role in mediating viral infection of pediatric airway epithelial cells in vitro.
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Acknowledgements
This work was supported by the University of Rochester Respiratory Pathogen Research Center NIH/NIAID, HHSN272201200005C, the LungMAP Consortium including 1U01HL122700, and the University of Rochester Pulmonary training grant T32-HL066988. We greatly appreciate the donor tissue, precious grifts generously given, supplied through the US DHHS Donation and Transplantation Network and the organizations that link donor families to the scientific community.
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Each author has met the Pediatric Research authorship requirements. C.S.A., E.E.W. and T.J.M. conceptualized the study. C.S.A., T.J.M., C.Y.-C., Q.W., E.E.W., J.A.M., Y.R. and G.S.P. designed the experiments. T.J.M., G.S.P. and R.M. developed the cohort and collected the specimens. C.S.A., K.D., T.J.M., C.Y.-C., J.M., Y.R. and S.B. generated, analyzed and interpreted the data. C.S.A., C.Y.-C., J.A.M., G.S.P., E.E.W. and T.J.M. wrote and/or revised the manuscript.
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Anderson, C.S., Chu, CY., Wang, Q. et al. CX3CR1 as a respiratory syncytial virus receptor in pediatric human lung. Pediatr Res 87, 862–867 (2020). https://doi.org/10.1038/s41390-019-0677-0
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DOI: https://doi.org/10.1038/s41390-019-0677-0
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