Replication of human noroviruses in stem cell–derived human enteroids

The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the leading cause of gastroenteritis worldwide. We report the successful cultivation of multiple HuNoV strains in enterocytes in stem cell-derived, nontransformed human intestinal enteroid monolayer cultures. Bile, a critical factor of the intestinal milieu, is required for strain-dependent HuNoV replication. Lack of appropriate histoblood group antigen expression in intestinal cells restricts virus replication, and infectivity is abrogated by inactivation (e.g., irradiation, heating) and serum neutralization. This culture…

• DL
  Dan L. Duncan Cancer Center, Baylor College of Medicine
• UP
  U.S. Public Health Service

  Awards: PO1 AI 057788, P30 CA-125123, P30 DK-56338
• NI
  National Institute of Allergy and Infectious Diseases

  Award: AI036211