BRIEF RESEARCH REPORT article

Front. Cell. Infect. Microbiol.

Sec. Molecular Viral Pathogenesis

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1597279

This article is part of the Research TopicPerspectives in Molecular Viral Pathogenesis: 2025View all 3 articles

Decoding Respiratory Syncytial Virus Morphology: Distinct Structural and Molecular Signatures of Spherical and Filamentous Particles

Provisionally accepted
  • 1Oregon State University, Corvallis, United States
  • 2Wake Forest University, Winston-Salem, North Carolina, United States

The final, formatted version of the article will be published soon.

Respiratory syncytial virus (RSV) is a pleomorphic enveloped virus that buds as both spherical and filamentous particles. The determinants of RSV particle morphology and the roles of these forms in transmission and pathogenicity are not clearly defined, owing to a complex interplay of viral proteins and host factors that remains poorly understood. To further characterize RSV morphology, we developed a sucrose gradient velocity sedimentation method to separate spherical and filamentous virions. Fluorescence microscopy and electron microscopy (EM) confirmed two distinct peaks containing predominantly spherical or filamentous particles, respectively. Notably, EM images revealed a distinctive "honeycomb" pattern on the RSV envelope, suggesting an ordered lattice of glycoproteins on the virion surface. Biochemical analyses of viral protein and lipid content showed that filamentous particles contained higher levels of uncleaved fusion protein F0 and exhibited distinct phospholipid profiles compared to spherical particles. Both forms were enriched in cholesterol and phospholipids characteristic of lipid rafts, consistent with the idea that RSV buds from lipid raft microdomains. This enrichment in raft lipids is linked to cell-to-cell fusion (syncytium) formation and virion assembly. Quantitative real-time PCR analysis indicated a high particle-to-PFU ratio (~4:1), meaning only about one in four RSV virions was infectious.Spherical particles contained on average ~3 genomic RNA copies per virion, whereas filamentous particles contained ~2 copies. These data reveal several structural and compositional differences between RSV particle morphologies that may influence viral pathogenesis, and they provide a foundation for new antiviral approaches targeting virion assembly and morphology.

Keywords: respiratory syncytial virus, Spherical particles, filamentous particles, morphology, sucrose gradient velocity sedimentation

Received: 20 Mar 2025; Accepted: 14 Apr 2025.

Copyright: © 2025 Pastey and Mccurdy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Manoj Kumar Pastey, Oregon State University, Corvallis, United States

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