The emergence and evolutionary advantage of the novel epidemic norovirus GII.17 lineage.

Human norovirus (HuNoV) is a major causative agent of non-bacterial gastroenteritis. During the winter of 2014/2015, the GII.17 Kawasaki variant emerged abruptly in Asia, temporarily surpassing the predominant GII.4 genotype and driving a significant epidemic surge. Since 2022, GII.17 has again caused sustained large-scale outbreaks due to the re-emerged of this genotype. To unravel the evolutionary advantages of these emerging GII.17 strains, we systematically evaluated the genetic variation mechanism of the GII.17 HuNoV capsid protein and their potential impact on viral prevalence. Phylogenetic analysis revealed that the novel GII.17 lineages originated from the clade C of GII.17, with an amino acid distance of 2.6% from clade C. This lineage was provisionally designated as C2. Its time of most recent common ancestor was 2020, with an average evolutionary rate of 5.47 × 10− 3 substitutions/site/year. Amino acid multiple sequence alignment analysis revealed that there were no new insertions or deletions in the C2 compared with the earlier variant C. Through the prediction of positive selection sites and B-cell epitopes, it was determined that the prevalence of C2 might not be due to an increase in epitopes but might be due to mutations in existing epitopes. Among 12 key amino acid mutations, sites 297, 374, and 409 in the P2 domain were the key amino acid sites for the prevalence of the new GII.17 lineage.