Comparison of human intestinal enteroid and zebrafish larva models for replication of human norovirus

= 5) replicated in both models showing a 1-2.5 log increase in HuNoV RNA. Of the 12 GII specimens tested, 8 replicated in the ZF model, and 7 replicated in the HIE model. Specimens that failed to replicate in each model were not the same, although most of them were GII.4 Sydney [P16]. One additional strain, GII.17[P17], replicated only in the ZF model. Across GII strains, viral RNA increases ranged from 1.6 to 3.3 log in the ZF model and from 0.4 to 3.68 log in the HIE model. These data highlight variability in HuNoV replication efficiency across models, potentially indicating the influence of model-specific factors on replication.IMPORTANCEHuman intestinal enteroid and zebrafish larva models have been independently shown to support replication of different strains of human norovirus (HuNoV), the leading cause of viral gastroenteritis worldwide. However, whether the same HuNoV-positive stool specimens replicate similarly in both systems has not been examined. In this study, stool specimens positive for a range of HuNoV genotypes were tested in both models. While specimens from the genogroup I (GI) genogroup consistently replicated in both systems, specimens from the GII genogroup showed variable replication, with some replicating in only one model and a couple of specimens not replicating in either model. These findings demonstrate that model-specific biological factors influence HuNoV replication and highlight the significance of using complementary model systems to better understand HuNoV pathogenesis.