title: The epithelial cell response to rotavirus infection.
abstract: Rotavirus is the most important worldwide cause of severe gastroenteritis in infants and young children. Intestinal epithelial cells are the principal targets of rotavirus infection, but the response of enterocytes to rotavirus infection is largely unknown. We determined that rotavirus infection of HT-29 intestinal epithelial cells results in prompt activation of NF-kappaB (<2 h), STAT1, and ISG F3 (3 h). Genetically inactivated rotavirus and virus-like particles assembled from baculovirus-expressed viral proteins also activated NF-kappaB. Rotavirus infection of HT-29 cells induced mRNA for several C-C and C-X-C chemokines as well as IFNs and GM-CSF. Mice infected with simian rotavirus or murine rotavirus responded similarly with the enhanced expression of a profile of C-C and C-X-C chemokines. The rotavirus-stimulated increase in chemokine mRNA was undiminished in mice lacking mast cells or lymphocytes. Rotavirus induced chemokines only in mice <15 days of age despite documented infection in older mice. Macrophage inflammatory protein-1beta and IFN-stimulated protein 10 mRNA responses occurred, but were reduced in p50-/- mice. Macrophage inflammatory protein-1beta expression during rotavirus infection localized to the intestinal epithelial cell in murine intestine. These results show that the intestinal epithelial cell is an active component of the host response to rotavirus infection.
authors.affiliation: Department of Medicine, Northport Veterans Affairs Medical Center, NY 11768, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Rollo
authors.forename: K P
authors.initials: KP
authors.lastname: Kumar
authors.forename: N C
authors.initials: NC
authors.lastname: Reich
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: J
authors.initials: J
authors.lastname: Angel
authors.forename: H B
authors.initials: HB
authors.lastname: Greenberg
authors.forename: R
authors.initials: R
authors.lastname: Sheth
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: B
authors.initials: B
authors.lastname: Oh
authors.forename: S J
authors.initials: SJ
authors.lastname: Hempson
authors.forename: E R
authors.initials: ER
authors.lastname: Mackow
authors.forename: R D
authors.initials: RD
authors.lastname: Shaw
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003967:Diarrhea / Q000276:immunology / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D005786:Gene Expression Regulation / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012367:RNA, Viral / Q000502:physiology; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology; D019895:Transposases / Q000172:deficiency / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; C499311:RAG2 protein, human; D012367:RNA, Viral; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; D019009:Proto-Oncogene Proteins c-kit; D019895:Transposases