Viral glycoproteins are the flexible keys to the cell. By changing shape, they open the cell so that the virus can enter. Libersou et al. show how one glycoprotein helps the vesicular stomatitis virus (VSV) gain access to mammalian cells.
Glycoprotein contortions reshape the viral and cellular membranes, allowing them to fuse. VSV carries a surface glycoprotein called G. Previous work indicated that G has at least three configurations—a pre-fusion state, an intermediate form that interacts with the target cell membrane, and a post-fusion conformation. Using electron microscopy and tomography, Libersou et al. tracked G to determine how its alterations spur fusion of VSV particles.
Instead of going in tip first, the virus, which is shaped like a bullet, backs in with its flat base. Low pH triggers the viruses to fuse and trips G molecules into the post-fusion arrangement. However, fusion requires more than gymnastics by G. The researchers found that if they reduced the pH just enough so that the glycoproteins distorted into the post-fusion shape, the viral particles remained locked out.
G undergoes another transformation—glycoproteins not located on the viral base interconnect to form helical arrays. The arrays can also reshape membranes, the researchers found. Libersou et al. conclude that fusion requires two rearrangements of G. First, glycoproteins on the viral base remodel and establish a connection with the cell membrane that initiates fusion. Then G molecules on the sides of the virus connect into helices that can deform the viral membrane to fully achieve fusion.
