Respiratory Syncytial virus glycoprotein G impedes CX3CR1-activation by CX3CL1 and monocyte function

The Respiratory Syncytial Virus (RSV) soluble G protein (sG) exhibits structural and functional similarities to the chemokine fractalkine (CX3CL1). It contains a mucin-like domain, a CX3C motif, and interacts with the CX3CR1 receptor expressed on immune and epithelial cells. This study aimed to elucidate the biological implications of RSV sG's interaction with CX3CR1. Wild-type (WT) and CX3C motif-deficient (CX3C mutant) RSV sG proteins were produced to evaluate their effects on CX3CR1 signaling in monocytic cells. While neither WT nor CX3C mutant sG directly activated CX3CR1 signaling, WT sG competitively inhibited CX3CL1 binding to CX3CR1. This inhibition reduced CX3CL1-induced CX3CR1 activation, monocyte migration, and adhesion. The CX3C motif was essential for this competitive blocking, as the CX3C mutant sG showed minimal impact on CX3CR1 functions. These findings suggest that RSV sG-mediated blockade of CX3CR1 signaling may help the virus evade host immune responses.
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