Structural heterogeneity of a human norovirus vaccine candidate

Human norovirus virus-like particles (VLPs) are assumed to be morphologically and antigenically similar to virion particles. The norovirus virion is assembled from 180 copies of the capsid protein (VP1) and exhibits T = 3 icosahedral symmetry. In this study, we showed that the vaccine candidate GII....

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2021-01, Vol.553, p.23-34
Main Authors: Devant, Jessica M., Hansman, Grant S.
Format: Article
Language:English
Subjects:
Animals
Antigens, Viral - immunology
Capsid Proteins - chemistry
Cryo-EM
Cryoelectron Microscopy
Epitopes
HEK293 Cells
Humans
Norovirus
Norovirus - chemistry
Norovirus - genetics
Norovirus - immunology
Sf9 Cells
Single-Domain Antibodies - immunology
Vaccine
Vaccines, Virus-Like Particle - chemistry
Vaccines, Virus-Like Particle - immunology
Vaccines, Virus-Like Particle - ultrastructure
Viral Vaccines - immunology
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Summary:Human norovirus virus-like particles (VLPs) are assumed to be morphologically and antigenically similar to virion particles. The norovirus virion is assembled from 180 copies of the capsid protein (VP1) and exhibits T = 3 icosahedral symmetry. In this study, we showed that the vaccine candidate GII.4c VP1 formed T = 1 and T = 3 VLPs, but mainly assembled into T = 4 icosahedral particles that were composed of 240 VP1 copies. In contrast, another clinically important genotype, GII.17, almost exclusively folded into T = 3 VLPs. Interestingly, the GII.4c T = 1 particles had higher binding capacities to norovirus-specific Nanobodies than to GII.4c T = 3 and T = 4 particles. Our data indicated that the occluded Nanobody-binding epitopes on the T = 1 particles were more accessible compared to the larger T = 3 and T = 4 particles. Overall, this new data revealed that GII.4c VLPs had a preference for forming the T = 4 icosahedral symmetry and future studies with varied sized norovirus VLPs should take caution when examining antigenicity. •First cryo-EM structure of a GII human norovirus vaccine candidate.•Norovirus vaccine GII.4 VLPs are composed of T = 1, T = 3, and T = 4 icosahedral particles.•GII.4 norovirus VLPs are predominantly T = 4 icosahedral particles.•Certain epitopes on T = 1 and T = 3/T = 4 particles are likely differently exposed.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2020.10.005