Biological and physico-chemical characterization of human norovirus-like particles under various environmental conditions.

Human noroviruses (HuNoVs) are the predominant etiological agent of viral gastroenteritis in all age groups worldwide. Mutations over the years have affected noroviruses' responses to environmental conditions due to the arrangement of amino acid residues exposed on the VP1 capsid surface of each strain. The GII.4 HuNoV genotype has been the predominant variant for decades, while the GII.17 genotype has often been detected in East Asia since 2014. Here, GII.17 and GII.4 baculovirus-expressed VLPs (virus-like particles) were used to study the biological (binding to HuNoV ligand, namely the ABO and Lewis antigens) and physicochemical properties (size, morphology, and charge) of the HuNoV capsid under different conditions (temperature, pH, and ionic strength). GII.17 showed stability at low and high ionic strength, while GII.4 aggregated at an ionic strength of 10 mM. The nature of the buffers influences the morphology and stability of the VLPs. Here, both VLPs were highly stable from pH 7-8.5 at 25 °C. VLPs retained HBGA binding capability for the pH, ionic strength and temperature encountered in the stomach (fed state) and the small intestine. Increasing the temperature to above 65 °C altered the morphology of VLPs, causing aggregation, and decreased their affinity to HBGAs. Comparing both isolates, GII.17 showed a better stability profile and higher affinity to HBGAs than GII.4, making them interesting candidate particles for a future norovirus vaccine. Biological and physicochemical studies of VLPs are as pertinent as ever in view of the future arrival of VLP-based HuNoV vaccines.

Epidemiological Impact of GII.17 Human Noroviruses Associated With Attachment to Enterocytes.

For the last 30 years, molecular surveys have shown that human norovirus (HuNoV), predominantly the GII.4 genotype, is one of the main causative agents of gastroenteritis. However, epidemiological surveys have revealed the worldwide emergence of GII.17 HuNoVs. Genetic analysis confirmed that GII.17 strains are distributed into three variants (i.e., Kawasaki 308, Kawasaki 323, and CS-E1). Here, virus-like particles (VLPs) were baculovirus-expressed from these variants to study putative interactions with HBGA. Qualitative analysis of the HBGA binding profile of each variant showed that the most recent and predominant GII.17 variant, Kawasaki 308, possesses a larger binding spectrum. The retrospective study of GII.17 strains documented before the emergence of the dominant Kawasaki 308 variant showed that the emergence of a new GII.17 variant could be related to an increased binding capacity toward HBGA. The use of duodenal histological sections confirmed that recognition of enterocytes involved HBGA for the three GII.17 variants. Finally, we observed that the relative affinity of recent GII.17 VLPs for HBGA remains lower than that of the GII.4-2012 variant. These observations suggest a model whereby a combination of virological factors, such as polymerase fidelity and increased affinity for HBGA, and immunological factors was responsible for the incomplete and non-persistent replacement of GII.4 by new GII.17 variants.