title: Comparative proteomic analyses of two reovirus T3D subtypes and comparison to T1L identifies multiple novel proteins in key cellular pathogenic pathways.
abstract: Viruses induce changes in the host to facilitate replication and evade the immune response. These changes are reflected by the host's proteome, including differences in protein abundance. Focusing on up and down regulated proteins after a virus infects the cell will lead to a characterization of the host response to infection, and may give insight into how viruses modulate proteins to evade host defense responses. We previously used SILAC to examine host proteomic changes in protein abundance in HEK293 cells infected with reovirus type 1, strain Lang (T1L). For the present study, we extended this analysis by determining cell protein alterations induced by two different reovirus subtypes, a less pathogenic type 3 Dearing (T3D(F)) isolate, and a more pathogenic isolate named T3D(C) that is presently in clinical trials as an anti-cancer oncolytic agent. This comparison of host proteome regulation showed that T3D(C) had a more marked effect on DNA replication proteins, recombination and repair, as well as immunological, apoptotic, and survival cell functions. We also identified several proteins not previously identified in any virus infection; branched chain amino-acid transaminase 2 (BCAT), paternally expressed 10 (PEG10), target of myb1 (TOM1), histone cluster 2 H4b (HIST2H4B) and tubulin beta 4B (TUBB4B).
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada, R3E 0J9.|Manitoba Center for Proteomics and Systems Biology, Room 799 John Buhler Research Centre University of Manitoba, Winnipeg, Canada, R3E 3P4.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Berard
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada, R3E 0J9.|National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington St., Winnipeg, Canada, R3E 3R2.
authors.forename: Alberto
authors.initials: A
authors.lastname: Severini
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada, R3E 0J9.|Manitoba Center for Proteomics and Systems Biology, Room 799 John Buhler Research Centre University of Manitoba, Winnipeg, Canada, R3E 3P4.|Manitoba Institute of Child Health, Room 641 John Buhler Research Center, University of Manitoba, Winnipeg, Canada, R3E 3P4.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Coombs
mesh_terms: D015153:Blotting, Western; D002853:Chromatography, Liquid / Q000379:methods; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012087:Reoviridae / Q000145:classification* / Q000502:physiology*; D012088:Reoviridae Infections / Q000378:metabolism* / Q000821:virology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D020543:Proteome; D014764:Viral Proteins
keywords: Bioinformatics pathways; Host cell response; Quantitative proteomics; RNA virus; SILAC