Respiratory syncytial virus glycoprotein G impedes CX(3)CR1-activation by CX(3)CL1 and monocyte function.

The soluble form of the Respiratory Syncytial Virus (RSV) G protein (sG) bears resemblance to the chemokine fractalkine (CX₃CL1). Both RSV sG and CX(3)CL1 possess a mucin-like domain and a CX(3)C motif, exist in membrane-associated and soluble forms, and bind to the CX₃CR1 receptor expressed on immune and epithelial cells. To explore the biological significance of RSV sG and CX₃CR1 interaction, we produced wild type (WT) and CX₃C motif-deficient (CX(3)C(Mut)) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CX(3)C(Mut)- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CX(3)CL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CX(3)CL1-mediated activation, as CX₃C(Mut) sG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses.