Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation.
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...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012873 |
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| author | Louis Kuijpers Evdokia-Anastasia Giannopoulou Yuzhen Feng Wouter van den Braak Abbas Freydoonian Ramon Ramlal Hugo Meiring Belén Solano Wouter H Roos Arjen J Jakobi Leo A van der Pol Nynke H Dekker |
| author_facet | Louis Kuijpers Evdokia-Anastasia Giannopoulou Yuzhen Feng Wouter van den Braak Abbas Freydoonian Ramon Ramlal Hugo Meiring Belén Solano Wouter H Roos Arjen J Jakobi Leo A van der Pol Nynke H Dekker |
| author_sort | Louis Kuijpers |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f89e7a67b13744b89b88d7453ddb52d4 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-f89e7a67b13744b89b88d7453ddb52d42025-02-08T05:30:30ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-02-01212e101287310.1371/journal.ppat.1012873Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation.Louis KuijpersEvdokia-Anastasia GiannopoulouYuzhen FengWouter van den BraakAbbas FreydoonianRamon RamlalHugo MeiringBelén SolanoWouter H RoosArjen J JakobiLeo A van der PolNynke H DekkerTo 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.https://doi.org/10.1371/journal.ppat.1012873 |
| spellingShingle | Louis Kuijpers Evdokia-Anastasia Giannopoulou Yuzhen Feng Wouter van den Braak Abbas Freydoonian Ramon Ramlal Hugo Meiring Belén Solano Wouter H Roos Arjen J Jakobi Leo A van der Pol Nynke H Dekker Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. PLoS Pathogens |
| title | Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. |
| title_full | Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. |
| title_fullStr | Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. |
| title_full_unstemmed | Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. |
| title_short | Enterovirus-like particles encapsidate RNA and exhibit decreased stability due to lack of maturation. |
| title_sort | enterovirus like particles encapsidate rna and exhibit decreased stability due to lack of maturation |
| url | https://doi.org/10.1371/journal.ppat.1012873 |
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