Global quantitative host proteomic assay of infected cells highlight virus specific protein changes and identify a novel role for secretogranin ii protein in virus infections

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dc.contributor.authorBerard, Alicia
dc.contributor.examiningcommitteeWilkins, John (Biochemistry & Medical Genetics) Feldmann, Heinz (Medical Microbiology) Duncan, Roy (Dalhousie University)en_US
dc.contributor.supervisorSeverini, Alberto (Medical Microbiology) Coombs, Kevin (Medical Microbiology)en_US
dc.date.accessioned2015-09-03T15:42:32Z
dc.date.available2015-09-03T15:42:32Z
dc.date.issued2012en_US
dc.date.issued2015-05-01en_US
dc.date.issued2015-06-15en_US
dc.degree.disciplineMedical Microbiologyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractViruses are obligate parasites that use the host cellular machinery to produce progeny virions. The host responds to this invading pathogen by induction of the immune system; however, the virus employs a variety of strategies to overcome these attacks. The complexity of the virus-host interaction is of great interest to researchers with aims to both characterize the relationship and target steps of the viral life cycle to hinder infection. Many targeted tactics employ single protein analysis; however, approaches that examine the whole set of virus/host interactions are available. Transcriptional alterations within host cells have been determined for many virus- host interactions by micro-array techniques; however little is known about the effects on cellular proteins. This study uses a quantitative mass spectrometric-based method, SILAC, to study differences in a host cell's proteome with infection by a virus. Mammalian reoviruses and herpes simplex viruses are prototypical viruses commonly studied to determine virus life cycle and interactions with hosts. Using three strains of reoviruses and one HSV1 strain, cells were infected to identify differentially regulated proteins at different times. Thousands of proteins were identified for each virus type, some up or down regulated after infection. Biological functions and network analyses were performed using online networking tools. These pathway analyses indicated numerous processes including cell death and inflammatory response are affected by T1L reovirus infection. Comparing reovirus strains revealed a greater overall proteomic change in host function when infected with the more pathogenic T3DC strain. For the HSV infection, host proteins altered during the different immediate early, earlyand late phases of infection helped characterize the host-virus interaction parallel to the virus life cycle. Overall, my study has characterized proteomic changes in different virus infection systems, identifying numerous novel cellular functional pathways and specific proteins altered during virus infections, specifically the secretogranin II protein that had opposite types of regulation in reoviruses and HSV and was examined for its effects on virus replication. Further studies on the novel proteomic characteristics may provide greater understanding to the complex virus-host interactome, leading to possible antiviral targets.en_US
dc.description.noteOctober 2015en_US
dc.identifier.citationProteomics. 2015 Jun;15(12):2113-35.en_US
dc.identifier.citationJ Proteome Res. 2015 May 1;14(5):2121-42.en_US
dc.identifier.citationPLoS One. 2012;7(12):e51939.en_US
dc.identifier.citationFuture Virology. 2012; 7(12):1193-1204.en_US
dc.identifier.urihttp://hdl.handle.net/1993/30717
dc.language.isoengen_US
dc.publisherACS Publicationsen_US
dc.publisherPLOSen_US
dc.publisherJohn Wiley and Sonsen_US
dc.publisherFuture Medicine Ltden_US
dc.rightsopen accessen_US
dc.subjectSILACen_US
dc.subjectReovirusen_US
dc.subjectHerpes simplex virus 1en_US
dc.subjectProteomicsen_US
dc.subjectHost-virus relationshipen_US
dc.subjectCell biologyen_US
dc.subjectMass spectrometryen_US
dc.subjectSystems biologyen_US
dc.titleGlobal quantitative host proteomic assay of infected cells highlight virus specific protein changes and identify a novel role for secretogranin ii protein in virus infectionsen_US
dc.typedoctoral thesisen_US
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