Evidence for a functional interaction between the respiratory syncytial virus fusion and attachment proteins in the envelope of infectious virus particles.

We have examined the interaction between the respiratory syncytial virus (RSV) F and G proteins on the surface of infected cells during multiple cycle infection using a low multiplicity of infection (MOI) model, and on the surface of virus particles that were isolated from infected cells. A combination of the proximity ligation assay (PLA) and confocal microscopy was used to demonstrate the interaction between the F and G proteins within the virus filaments on infected cells. Co-precipitation of the F and G proteins was confirmed using detergent extracts prepared from infected cells and in detergent extracts prepared from purified virus particles. The influence of the G protein in mediating virus spread in the low MOI model was further examined using the recombinant virus isolates rg224RSV (that expresses all virus proteins) and rg224RSV-{Delta}G (which does not express the G protein). While cells could be initially infected by both viruses, the rg224RSV-{Delta}G virus exhibited severely impaired localised virus transmission in the multiple cycle infection assay. Collectively these data provide evidence that the F and G proteins interact within the envelope of RSV particles, and suggests that this interaction may promote virus transmission. The interaction between these proteins in a single protein complex represents a potential new target for the development of antivirus strategies and in the development of RSV vaccine candidates.