New images of respiratory syncytial virus from researchers at the University of Wisconsin–Madison may hold the key to preventing or slowing RSV infections.
Using an imaging technique called cryo-electron tomography, Elizabeth Wright, a UW–Madison biochemistry professor, and her team have now revealed details of molecules and structures essential to RSV’s form and function. They published their findings recently in Nature.
Cryo-ET freezes viral particles or other molecules at ultracold temperatures, stopping biological processes in action. This allows researchers to examine the structures of organisms, cells and organelles, and viruses and capture small-scale images of structures frozen in time. Flash-freeze many RSV particles, and cryo-ET imaging will capture (nearly) all the virus’s possible configurations from many different angles. These 2D images are combined to produce a representation of the virus’s 3D structures at high resolutions — even at the level of individual atoms.
Wright’s recent study produced high-resolution images detailing the structure of two RSV proteins, RSV M protein and RSV F protein, that are crucial to the interaction between the virus and the host cell membrane. Both proteins are also present in related viruses.
RSV M protein interacts with host cell membranes, holding together the virus’s filamentous structure and coordinating viral components and other proteins — including RSV F proteins. RSV F proteins sit on the viral surface, ready to engage with host cell receptors and regulate the virus’s fusion and entry into the host cell. The scientists’ images reveal that in RSV, two F proteins come together to form a more stable unit. Wright says that this association may prevent the F proteins from prematurely infecting the host cell.
The scientists believe that F protein pairs may be a key to destabilizing the virus before it is ready to infect its next host, making pairs of F proteins a possible target for future drug development. They will continue to explore how RSV proteins interact with each other to cause infection.
