HKUMed Organoid Experiments Show JN.1 Replicates Preferentially in Proximal Intestinal Enteroids Over Respiratory Tissues

Researchers at HKUMed directly infected matched sets of airway organoids, alveolar epithelial cells, proximal intestinal enteroids, and colon monolayers with representative Omicron sublineages under identical conditions. This design isolated intrinsic viral properties from confounding population immunity. EG.5.1 and XBB.1.5 reached peak titers fastest in lower-airway models and exploited dual entry pathways, whereas JN.1 showed the opposite pattern: modest respiratory replication but significantly elevated growth in proximal enteroids without corresponding colon-cell preference.

The intestinal adaptation of JN.1 coincided with reduced innate immune activation, raising the possibility of prolonged asymptomatic shedding via feces. Prior observational data from wastewater and stool PCR surveys have already documented prolonged viral RNA in convalescent patients, yet functional confirmation in primary human tissue was previously lacking. The current findings therefore supply a mechanistic bridge between genomic surveillance signals and potential non-respiratory transmission routes.

Public-health planning must now weigh whether routine respiratory-focused metrics will under-detect lineages optimized for gut persistence. Ongoing functional characterization of emerging subvariants remains essential because immune landscapes continue to shift and small changes in tropism can alter outbreak dynamics. Next studies should quantify fecal shedding duration and infectiousness in controlled human-challenge or household cohorts.