Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation.

Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. When disturbed by AGE, Gammaproteobacteria dominated, particularly Pseudomonas species. Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness.

Norovirus is a leading cause of acute gastroenteritis (AGE) worldwide, with significant morbidity and mortality, particularly in young children and older adults. This study characterizes the global prevalence and diversity of norovirus genotypes among sporadic cases. A review of English-language studies (published 2002–2026) that characterized norovirus genotype distribution among sporadic cases was conducted, excluding outbreak and asymptomatic detections. Pooled data were analyzed with stratifications by age group, region, and year of sample collection. A total of 20,588 cases were identified from 72 publications. There were 30 genotypes identified, with GII.4, GII.3, GII.2, GII.17, and GII.6 and each accounting for ≥5% of detections. GII.4 was the predominant genotype globally, accounting for 54% of cases and up to 80% among older adults across all years, but periodic fluctuation was seen, coinciding with fluctuations in the prevalence of other genotypes, especially GII.3, GII.2, and GII.17. Among GI genotypes, GI.3 was most prevalent (46%), particularly among adults. Genotype diversity was highest among children in low- and middle-income countries and in Asia/Oceania. Findings indicate that a small number of genotypes account for most cases. As genotyping characterizes the major capsid protein, the primary target of antibody recognition, findings have important implications for vaccine development and public health interventions.