Study Sheds Light on RSV Structural Protein Organization, Paving the Way for Vaccine Improvements

A new study published in Nature Communications has provided crucial insights into the structure and organization of respiratory syncytial virus (RSV).

RSV, a highly pleomorphic virus responsible for over 3 million hospitalizations annually, has been the focus of ongoing research due to its severe impact on both children and adults. Although the US Food and Drug Administration recently approved two vaccines targeting the RSV fusion (F) protein, further research is necessary to develop effective treatments for all at-risk populations.

“In this work we present high-resolution sub-tomogram averages of the RSV M lattice that clearly illustrate that the helical-like lattice is composed of an extended network of M-dimers,” explained Bryan Sibert, PhD, Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, and coauthors.

The scientists used advanced cryo-electron tomography (cryo-ET) to analyze RSV virions at a molecular level. They discovered that the F protein, a key target for vaccine development, is organized in rows and often forms pairs, known as "dimer-of-trimers," on the virus surface. These pairs are arranged in an antiparallel fashion, suggesting specific interactions between the F trimers that could influence the virus’s ability to infect cells.

Additionally, the study revealed the presence of a lattice-like structure formed by the RSV matrix (M) protein beneath the viral membrane. This M protein lattice is crucial for virion assembly and the structural integrity of the virus. Subtomogram averaging allowed the researchers to model the M-dimer structure with high resolution, confirming the arrangement of the lattice and its interaction with the F protein on the surface.

The findings suggest that the spatial relationship between the F and M proteins is coordinated, highlighting a critical aspect of RSV structural organization.

“These results provide insight into RSV virion organization and may aid in the development of RSV vaccines and anti-viral targets,” concluded the study authors.

Reference

Sibert BS, Kim JY, Yang JE, et al. Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers. Nat Commun. 2024;15(1):5923. doi:10.1038/s41467-024-50162-x