Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

RNA, Viral*/genetics ; RNA, Viral*/metabolism ; Virion*/ultrastructure ; Virion*/genetics ; Vaccines, Virus-Like Particle*/immunology ; Enterovirus*/genetics ; Enterovirus*/immunology; Capsid/ultrastructure ; Capsid/metabolism ; Animals ; Humans ; Cryoelectron Microscopy ; Enterovirus Infections

Competing Interests: The authors have declared that no competing interests exist.
To counteract hand, foot, and mouth disease-causing viruses such as enterovirus A71 and coxsackievirus A6, virus-like particles (VLPs) have emerged as a leading contender for the development of a multivalent vaccine. However, VLPs have shown rapid conversion from a highly immunogenic state to a less immunogenic state and low particle integrity lifetimes compared to inactivated virus vaccines, thus raising concerns about their overall stability. Here, we produce VLPs to investigate capsid stability using cryogenic electron microscopy (cryo-EM), mass spectrometry (MS), biochemical assays, and atomic force microscopy (AFM). In contrast to prior studies and prevailing hypotheses, we show that insect-cell produced enterovirus VLPs include encapsidated RNA fragments with viral protein coding sequences. Our integrated approach reveals that CVA6 VLPs do not undergo viral maturation, in contrast to virions; that they can encapsidate RNA fragments, similarly to virions; and that despite the latter, they are more brittle than virions. Interestingly, this indicates that CVA6 VLP stability is more affected by lack of viral maturation than the presence of RNA. Our study highlights how the development of VLPs as vaccine candidates should encompass probing for unwanted (viral) RNA content and establishing control of their maturation to enhance stability.
(Copyright: © 2025 Kuijpers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (RNA, Viral)
0 (Vaccines, Virus-Like Particle)

Date Created: 20250204 Date Completed: 20250505 Latest Revision: 20250505

20250505

PMC11793780

10.1371/journal.ppat.1012873

39903789