Helical ordering of envelope-associated proteins and glycoproteins in respiratory syncytial virus

Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Here, using cryogenic electron microscopy and tomography combined with computational image analysis and three-dimensional reconstruction, we show that there is extensive helical ordering of the envelope-associated proteins and glycoproteins of RSV filamentous virions. We calculated a 16 angstrom resolution sub-tomogram average of the matrix protein (M) layer that forms an endoskeleton below the viral envelope. These data define a helical lattice of M-dimers, showing how M is oriented relative to the viral envelope. Glycoproteins that stud the viral envelope were also found to be helically ordered, a property that was coordinated by the M-layer. Furthermore, envelope glycoproteins clustered in pairs, a feature that may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV virions. These data provide molecular insight into the organisation of the virion and the mechanism of its assembly.

Automated summary

The study found that the envelope-associated proteins and glycoproteins of RSV filamentous virions exhibit extensive helical ordering, with a helical lattice of M-dimers forming an endoskeleton below the viral envelope. The clustered pairs of envelope glycoproteins, coordinated by the M-layer, may have implications for the conformation of fusion glycoprotein epitopes. The presence of N-RNA rings packaged within RSV virions in authentic virus infections provides molecular insight into the organization of the virion and the mechanism of its assembly.