title: Rotavirus infection activates the UPR but modulates its activity.
abstract: BACKGROUND
  Rotaviruses are known to modulate the innate antiviral defense response driven by IFN. The purpose of this study was to identify changes in the cellular proteome in response to rotavirus infection in the context of the IFN response. We also sought to identify proteins outside the IFN induction and signaling pathway that were modulated by rotavirus infection.
  
  
  METHODS
  2D-DIGE and image analysis were used to identify cellular proteins that changed in levels of expression in response to rotavirus infection, IFN treatment, or IFN treatment prior to infection. Immunofluorescence microscopy was used to determine the subcellular localization of proteins associated with the unfolded protein response (UPR).
  
  
  RESULTS
  The data show changes in the levels of multiple proteins associated with cellular stress in infected cells, including levels of ER chaperones GRP78 and GRP94. Further investigations showed that GRP78, GRP94 and other proteins with roles in the ER-initiated UPR including PERK, CHOP and GADD34, were localized to viroplasms in infected cells.
  
  
  CONCLUSIONS
  Together the results suggest rotavirus infection activates the UPR, but modulates its effects by sequestering sensor, transcription factor, and effector proteins in viroplasms. The data consequently also suggest that viroplasms may directly or indirectly play a fundamental role in regulating signaling pathways associated with cellular defense responses.
authors.affiliation: Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59718, USA.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Zambrano
authors.forename: Khalil
authors.initials: K
authors.lastname: Ettayebi
authors.forename: Walid S
authors.initials: WS
authors.lastname: Maaty
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Faunce
authors.forename: Brian
authors.initials: B
authors.lastname: Bothner
authors.forename: Michele E
authors.initials: ME
authors.lastname: Hardy
mesh_terms: D000818:Animals; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D000882:Haplorhini; D054884:Host-Pathogen Interactions; D007371:Interferon-gamma / Q000276:immunology*; D008856:Microscopy, Fluorescence; D020543:Proteome / Q000032:analysis*; D012401:Rotavirus / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000276:immunology* / Q000473:pathology*; D056811:Unfolded Protein Response
chemical_list: D020543:Proteome; D007371:Interferon-gamma