Since electron micrographs first revealed the bullet-shaped morphology of vesicular stomatitis virus (a virus related to rabies virus), understanding the architecture has been elusive. It was known that the RNA genome is wrapped in a helical structure by the viral nucleocapsid (N) protein, but how this structure was encased by the viral matrix (M) protein and the envelope was not clear. These questions have been elegantly answered by a new model of the VSV virion determined by cryo-electron microscopy.
The RNA genome of VSV is coated with many copies of the N protein to form a nucleocapsid with helical symmetry. The nucleocapsid is in turn surrounded by the M protein and then the viral membrane. The reconstructed image (right) not only shows the helical nature of the N protein – RNA assembly, but reveals that the M protein also forms an outer helix. The inner and outer helices are aligned by interactions between N and M protein subunits. Consequently the virion is more rigid than enveloped viruses of other families, such as influenza viruses.
Both the inner (purple) and outer (magenta) lipid bilayers of the virion are visible in the reconstructed image. Close inspection of the inner leaflet (left) reveals that part of the envelope contacts each M protein subunit. In this area is a thin line that may represent part of the G glycoprotein that passes through the membrane. Virions attach to cell receptors via the G glycoprotein, which is embedded in the viral membrane. The interaction of G protein with M, known to be important for budding of viral particles, can now be visualized.
The VSV nucleocapsid contains 37.5 N protein subunits per helical turn, except near the bullet-shaped tip. The structure reveals that the angle of the N protein changes markedly to allow insertion of fewer subunits per turn. Assembly of the nucleocapsid probably begins at the tip of the bullet, as the 5′-end of the viral RNA genome becomes bound with N proteins. Six coils of larger diameter are formed, and then the angle of the N proteins change so that each ring contains 37.5 subunits.
These revealing new data are made even more beautiful in this movie, which shows the virion trunk rotated first around the helical axis, then around the horizontal axis. Parts of the membrane and the M and N protein helices have been removed to reveal the virion interior. The viral RNA is not visible as it is smaller than the resolution of the reconstructed image.