Atomic structure of the predominant GII.4 human norovirus capsid reveals novel stability and plasticity

Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E. Crowe, Robert L. Atmar, Mary K. Estes and B. V. Venkataram Prasad ()
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Liya Hu: Baylor College of Medicine
Wilhelm Salmen: Baylor College of Medicine
Rong Chen: Baylor College of Medicine
Yi Zhou: Baylor College of Medicine
Frederick Neill: Baylor College of Medicine
James E. Crowe: Vanderbilt University Medical Center
Robert L. Atmar: Baylor College of Medicine
Mary K. Estes: Baylor College of Medicine
B. V. Venkataram Prasad: Baylor College of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, and GII.4 virus-like particles (VLPs) are being used in vaccine development. The atomic structure of the GII.4 capsid in the native T = 3 state has not been determined. Here we present the GII.4 VLP structure with T = 3 symmetry determined using X-ray crystallography and cryo-EM at 3.0 Å and 3.8 Å resolution, respectively, which reveals unanticipated novel features. A novel aspect in the crystal structure determined without imposing icosahedral symmetry is the remarkable adaptability of the capsid protein VP1 driven by the flexible hinge between the shell and the protruding domains. In both crystal and cryo-EM structures, VP1 adopts a stable conformation with the protruding domain resting on the shell domain, in contrast to the ‘rising’ conformation observed in recent cryo-EM structures of other GII.4 VLPs. Our studies further revealed that the resting state of VP1 dimer is stabilized by a divalent ion, and chelation using EDTA increases capsid diameter, exposing new hydrophobic and antigenic sites and suggesting a transition to the rising conformation. These novel insights into GII.4 capsid structure, stability, and antigen presentation may be useful for ongoing vaccine development.

Date: 2022
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DOI: 10.1038/s41467-022-28757-z

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