Enteric bacteria promote human and mouse norovirus infection of B cells

Science. 2014 Nov 7;346(6210):755-9. doi: 10.1126/science.1257147.


The cell tropism of human noroviruses and the development of an in vitro infection model remain elusive. Although susceptibility to individual human norovirus strains correlates with an individual's histo-blood group antigen (HBGA) profile, the biological basis of this restriction is unknown. We demonstrate that human and mouse noroviruses infected B cells in vitro and likely in vivo. Human norovirus infection of B cells required the presence of HBGA-expressing enteric bacteria. Furthermore, mouse norovirus replication was reduced in vivo when the intestinal microbiota was depleted by means of oral antibiotic administration. Thus, we have identified B cells as a cellular target of noroviruses and enteric bacteria as a stimulatory factor for norovirus infection, leading to the development of an in vitro infection model for human noroviruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology*
  • Caliciviridae Infections / immunology*
  • Caliciviridae Infections / microbiology
  • Caliciviridae Infections / virology
  • Cell Line
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / physiology*
  • Gastroenteritis / immunology*
  • Gastroenteritis / microbiology
  • Gastroenteritis / virology
  • Genome, Viral / genetics
  • Genome, Viral / physiology
  • Homeodomain Proteins / genetics
  • Humans
  • Intestines / immunology
  • Intestines / microbiology*
  • Mice
  • Mice, Mutant Strains
  • Norovirus / physiology*
  • Peyer's Patches / immunology
  • Peyer's Patches / virology
  • Virus Replication*


  • Anti-Bacterial Agents
  • Homeodomain Proteins
  • RAG-1 protein