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

Abstract

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 A 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.

Importance of RNA length for in vitro encapsidation by the nucleoprotein of human respiratory syncytial virus

“…Further characterisation of IBs morphogenesis in the presence of RSV helical NC should be of great interest, as the size and high flexibility of these structures could modulate IBs morphogenesis. A recent cryo-electron tomography study of RSV infected cells has revealed the presence of N rings in filamentous RSV particles (57), showing for the first time the heterogeneity of N assembly in the cell. The role of these structures during viral cycle i.e.…”

In Vitro Study of Rna Encapsidation by the Nucleoprotein of Human Respiratory Syncytial Virus

“…Further characterisation of IBs morphogenesis in the presence of RSV helical NC should be of great interest, as the size and high flexibility of these structures could modulate IBs morphogenesis. Of note, a recent cryo-electron tomography study of RSV infected cells has revealed the presence of N rings in filamentous RSV particles (55), showing for the first time the heterogeneity of N assembly in the cell. The role of these structures during viral cycle i.e.…”

Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles

“…They also lacked the long-range helical ordering typical of RSV glycoproteins (Extended Data Fig. 3c,e) 23 . We designated these structures 'pseudotyped viruses' (Extended Data Fig.…”