Researchers at the University of Wisconsin–Madison have produced the most detailed images of respiratory syncytial virus (RSV), potentially opening the door to targeted RSV Protein Structures and therapies for a virus that hospitalizes hundreds of thousands in the U.S. annually.
The findings, recently published in Nature, reveal the virus’s complex structure in unprecedented detail and could help researchers identify new drug targets to prevent or reduce severe infections.
A Complex Viral Structure Hinders Treatment for RSV Protein Structures
RSV poses a significant risk to young children, older adults, and individuals with chronic respiratory conditions. Despite its widespread impact, effective treatment options remain limited. In the United States, RSV vaccines are currently approved only for pregnant women and older adults, while prophylactic treatments are available primarily for infants.
One of the significant challenges in developing RSV therapies lies in the virus’s unusual shape. Unlike other common respiratory viruses, RSV consists of tiny, flexible filaments that have made it difficult to identify stable protein structures — the kinds of structures drug developers need to design effective antivirals.
“There are several viruses related to RSV that are also significant human pathogens, including measles,” said Elizabeth Wright, professor of biochemistry at UW–Madison. “What we know about related viruses gives us clues, but to identify drug targets, we need a closer look at RSV proteins intimately associated with host cell membranes.”
Cryo-Electron Tomography Offers New Insights
Wright and her team turned to cryo-electron tomography (cryo-ET), a high-resolution imaging technique that flash-freezes viral particles at extremely low temperatures. This method captures snapshots of the virus in its natural, functional state, allowing researchers to assemble 3D representations from 2D images taken at multiple angles.
Using cryo-ET, the researchers closely examined two proteins critical to RSV’s ability to infect host cells: the M (matrix) protein and the F (fusion) protein. The RSV M protein helps maintain the virus’s filamentous shape and organizes other viral components. The RSV F protein on the virus’s surface enables the virus to attach to and fuse with host cells. RSV Protein Structures.
Their findings revealed that RSV F proteins form stable pairs — a structural arrangement that may help prevent premature fusion with host cells. “Our primary findings reveal structural details that allow us to understand better not only how the protein regulates assembly of viral particles, but also the coordination of proteins that enable the virus to be infectious,” Wright said.
A New Target for Future Therapies
The discovery of the RSV F protein pairing may have significant implications for antiviral drug development. Researchers believe destabilizing these protein pairs could stop the virus from initiating infection, offering a promising new treatment pathway.
Furthermore, both the M and F proteins appear in other viruses, such as measles, suggesting that these findings could help advance treatments for a broader group of respiratory pathogens.
Wright’s team will continue studying the interactions between RSV proteins to understand better how the virus assembles and becomes infectious. While vaccines have already made strides in protecting vulnerable populations, the detailed imagery available may allow scientists to develop the first generation of targeted RSV therapies.
Reference: Bryan S. Sibert, Joseph Y. Kim, Jie E. Yang, Zunlong Ke, Christopher C. Stobart, Martin L. Moore, Elizabeth R. Wright. Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers. Nature Communications, 2024.
