Molecular Evolution and Epidemiology of Norovirus GII.4 Viruses in the United States.

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 Sydney[P31] dominated followed by GII.4 Sydney[P16] from 2016-2020, and the new sub-lineage GII.4 Sydney[P16]-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.