Coronavirus spherules are supported by a novel triple-layer protein lattice
- 1The Pirbright Institute
Abstract
Coronaviruses (CoVs) cause significant disease in humans and animals, with a track-record of cross-species transmission. Despite their global significance, available control strategies are limited, especially for emerging CoVs. A deeper fundamental understanding of the virus life cycle is essential to underpin development of control measures. A critical step of the CoV life cycle is the rearrangement of host cell membranes into replication organelles (ROs). This is conserved across all CoVs and ROs comprise double membrane vesicles (DMVs), the site of viral RNA synthesis, and double membrane spherules. CoV spherules are complex structures requiring both positive and negative curvature of paired membranes so are predicted to have a high energy cost to maintain. To date they have an entirely unknown function. Interestingly, although always present, abundance of spherules in CoV infected cells varies with Betacoronavirus Middle East Respiratory Syndrome coronavirus, Gammacoronavirus infectious bronchitis virus (IBV) and porcine deltacoronavirus in particular producing a considerable number. Here, using cryo-bioimaging we identified for the first time that CoV spherules are embedded with a complex and organised triple-layered protein lattice and that spherules always contain a cargo that appears arranged as a shell inside the vesicle. In addition, we confirmed the presence of a double membrane spanning molecular pore in Gammacoronavirus DMVs and further identified a population of potential DMV formation intermediates. Together, this work provides a foundation for understanding a fundamental yet unresolved aspect of coronavirus replication.
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BibTeX
@misc{phillips2026coronavirus,
title = {{Coronavirus spherules are supported by a novel triple-layer protein lattice}},
author = {P. M. Phillips and J. Wells and N. Mathew and N. Doyle and S. Keep and P. Majumder and J. B. Gilchrist and P. C. Hawes and J. Grimes and M. Harkiolaki and D. K. Clare and H. J. Maier},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757900},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757900v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Coronavirus spherules are supported by a novel triple-layer protein lattice
AU - P. M. Phillips
AU - J. Wells
AU - N. Mathew
AU - N. Doyle
AU - S. Keep
AU - P. Majumder
AU - J. B. Gilchrist
AU - P. C. Hawes
AU - J. Grimes
AU - M. Harkiolaki
AU - D. K. Clare
AU - H. J. Maier
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757900
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757900v1
AB - Coronaviruses (CoVs) cause significant disease in humans and animals, with a track-record of cross-species transmission. Despite their global significance, available control strategies are limited, especially for emerging CoVs. A deeper fundamental understanding of the virus life cycle is essential to underpin development of control measures. A critical step of the CoV life cycle is the rearrangement of host cell membranes into replication organelles (ROs). This is conserved across all CoVs and ROs comprise double membrane vesicles (DMVs), the site of viral RNA synthesis, and double membrane spherules. CoV spherules are complex structures requiring both positive and negative curvature of paired membranes so are predicted to have a high energy cost to maintain. To date they have an entirely unknown function. Interestingly, although always present, abundance of spherules in CoV infected cells varies with Betacoronavirus Middle East Respiratory Syndrome coronavirus, Gammacoronavirus infectious bronchitis virus (IBV) and porcine deltacoronavirus in particular producing a considerable number. Here, using cryo-bioimaging we identified for the first time that CoV spherules are embedded with a complex and organised triple-layered protein lattice and that spherules always contain a cargo that appears arranged as a shell inside the vesicle. In addition, we confirmed the presence of a double membrane spanning molecular pore in Gammacoronavirus DMVs and further identified a population of potential DMV formation intermediates. Together, this work provides a foundation for understanding a fundamental yet unresolved aspect of coronavirus replication.
ER -