Respiratory syncytial virus glycoprotein G impedes CXCR1-activation by CXCL1 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 CXCL1 possess a mucin-like domain and a CXC 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 (CXC) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CXC- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CXCL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CXCL1-mediated activation, as CX₃C sG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses.