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

In this study we have examined the interaction between the respiratory syncytial virus (RSV) F and G proteins on both the surface of infected cells using a low multiplicity of infection (MOI) model (MOI of 0.0001) and on the surface of virus particles. 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 and rg224RSV-ΔG (which does not express the G protein). While virus particles were formed by both viruses, the rg224RSV-ΔG virus exhibited severely impaired localised virus transmission using the low MOI model. Collectively these data provide evidence that the F and G proteins interact within the envelope of RSV particles, and that this interaction promotes virus transmission is suggested. 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.