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BACKGROUND: Noroviruses are the leading cause of acute gastroenteritis worldwide, with GII.4 Sydney viruses responsible for the majority of infections until 2023. METHODS: To study the evolutionary dynamics of GII.4 noroviruses in the United States (2011-2023), we sequenced and analyzed 406 VP1 and 335 RNA-dependent RNA polymerase sequences submitted to CaliciNet. RESULTS: Time-scale analysis showed that the average evolutionary rate of GII.4 strains was 5.56 × 10-3 substitutions per site per year. GII.4 Sydney viruses circulated throughout the entire study period albeit with 4 polymerase types (GII.P31, GII.P16, GII.P4 and GII.P12). From 2011-2015, GII.4 SydneyP31 dominated followed by GII.4 SydneyP16 from 2016-2020, and the new sub-lineage GII.4 SydneyP16-2020 from 2021-to present. Since 2017, we observed the emergence of 3 novel GII.4 clusters based on amino acids in VP1: GII.4 San Francisco, GII.4 Allegany, and GII.4 Wichita. GII.4 San Francisco and GII.4 Allegany had a GII.P31 RNA-dependent RNA polymerase, whereas GII.4 Wichita strains had GII.P4. GII.4 Allegany and GII.4 Wichita exhibited major amino acid substitutions in epitopes A to E, G, and H, while GII.4 San Francisco viruses have an alanine insertion in epitope A. GII.4 Allegany and GII.4 Wichita virus-like particles bound porcine gastric mucin at a similar level as GII.4 New Orleans and GII.4 Sydney. However, blocking of binding to virus-like particles by human serum pools demonstrated that their antigenicity was significantly different. CONCLUSIONS: We identified 3 new GII.4 noroviruses cocirculating with GII.4 Sydney. Early detection of new strains will aid in tracking their spread and assessing their pandemic potential.
Barclay et al. (Wed,) studied this question.