CX3CR1 as a Respiratory Syncytial Virus Receptor in Pediatric Human Lung
Christopher S Anderson,
Jared A. Mereness,
Ravi S Misra,
Edward E. Walsh,
Thomas J. Mariani
Posted 16 Sep 2019
medRxiv DOI: 10.1101/19002394
Posted 16 Sep 2019
BACKGROUNDData 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. METHODSCX3CR1 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. RESULTSLow 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. CONCLUSIONCX3CR1 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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