Thus, this mutation, or other mutations that block binding to CX3CR1, has the potential to improve a live attenuated RSV vaccine by attenuating both infection and disease pathogenesis.
Comparison of these structures with the structure of fractalkine (CX3CL1) alone or in complex with a viral homolog of CX3CR1 (US28) suggests that RSV G would bind to CX3CR1 in a mode that is distinct from that of fractalkine.
Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A<sup>186</sup>, within the CX3C motif, mutating it to CX4C (<sup>182</sup>CWAIAC<sup>187</sup>), which is known to block binding to CX3CR1, might decrease disease.
We studied the role of CX3CR1 in RSV infection with CX3CR1-transfected cell lines and HAECs with variable percentages of CX3CR1-expressing cells, and the effect of anti-CX3CR1 antibodies or a mutation in the RSV CX3C motif.
Our findings support the hypothesis of the pivotal role of the G glycoprotein CX3CR1 pathway in the pathogenesis of RSV bronchiolitis and propose CX3CR1 as a potential therapeutic target.