Overcoming host restrictions to enable continuous passaging of GII.3 human norovirus in human intestinal enteroids.

ABSTRACT: The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed one consensus change in the major capsid protein and several dynamic adaptation

SUBMITTER: Kaur G 

PROVIDER: S-EPMC12871457 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature