Epidemiology and molecular evolution of norovirus GII.17 in the United States, 2021-2025

GII.4 noroviruses have been the leading cause of acute gastroenteritis outbreaks in the United States (U.S.) for the past decade. Recently, GII.17 viruses have emerged globally, raising concerns about changes in disease burden and potential replacement of GII.4 as the predominant strain.

We characterized molecular and epidemiological features of U.S. GII.17 norovirus outbreaks from September 2021-August 2025 submitted to CaliciNet. Norovirus-positive outbreak samples were sequenced followed by RdRp and VP1 phylogenetic analyses. CaliciNet and National Outbreak Reporting System data were linked to compare GII.17 and GII.4 epidemiologic and clinical characteristics. Virus-like particles binding to gastric mucin and antibody blockade assays were conducted to assess antigenic variation among GII.17 variants.

Among 1,412 outbreaks, GII.17 prevalence increased from 5.0% (2021-2022) to 74.8% (2024-2025). Compared with GII.4, GII.17 was more frequently reported with foodborne exposure (16.4% vs 9.6%), affected persons aged 10-49 years compared with other groups (31.1% vs 23.1%), and associated with slightly higher rates of vomiting (78.2% vs 72.2%), abdominal cramps (34.2% vs 30.1%), and fever (15.9% vs 10.9%). Phylogenetic analysis detected GII.17[P17] Romania-like (93.3%) followed by GII.17[P17] Kawasaki308-like strains (4.6%) and two novel tentative variants: Santa Clara (1.3%) and London (0.1%). Despite substitutions in key P2 antigenic sites, surrogate antibody neutralization remained conserved.

These findings indicate a recent shift in norovirus genotype dominance in the U.S., likely driven by enhanced transmissibility or population susceptibility rather than increased virulence. Continued molecular surveillance is essential to monitor viral evolution and public health impact of norovirus.