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dc.contributor.authorWan, Stephanie
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2014-01-23 10:55:16.715en
dc.date.accessioned2014-01-23T19:48:29Z
dc.date.available2014-01-23T19:48:29Z
dc.date.issued2014-01-23
dc.identifier.urihttp://hdl.handle.net/1974/8580
dc.descriptionThesis (Master, Microbiology & Immunology) -- Queen's University, 2014-01-23 10:55:16.715en
dc.description.abstractIn response to viral infection, host cells activate various antiviral defence mechanisms to inhibit virus replication. Therefore in order for a virus to replicate efficiently, it must counteract cellular antiviral defence. Promyelocytic leukemia protein (PML) is a cellular protein involved in intrinsic immunity. It inherently forms nuclear bodies (PML-NBs) that assemble at the site of viral genomes. Proteins related to epigenetic regulation are recruited to PML-NBs, and silence viral gene transcription. This study focuses on the role of two herpes simplex virus type 2 (HSV-2) proteins, ICP0 and Us3, in disrupting PML-NBs and counteracting cellular antiviral defence. En passant mutagenesis was used to create recombinant HSV-2 viruses lacking ICP0, Us3, or both ICP0 and Us3. Growth analysis of these recombinants indicates no growth defects for the ICP0Δ virus, while the Us3Δ virus grows to one log lower titres than wild type virus (WT). By contrast, the ICP0Δ virus displays a delay in PML-NB disruption, but the Us3Δ virus is as efficient as WT. However, Us3 is still important for PML-NB disruption, since the ICP0Δ/Us3Δ double mutant exhibits a greater delay than the ICP0Δ single mutant. Although PML is a mediator of the interferon (IFN) response and it was predicted that ICP0 and Us3 interfere with the IFN response through disruption of PML-NBs, my results show that only some HSV-2 Us3Δ clones are hypersensitive to the effects IFN, and others are resistant. Us3 affects more than one cellular pathway, and those cellular pathways are affected by more than one viral protein. I conclude that the activities of multiple viral proteins create a fine balance between activating cellular pathways to promote virus replication, and inhibiting cellular antiviral defence.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectUs3en_US
dc.subjectHerpesvirusen_US
dc.subjectintrinsic immunityen_US
dc.subjectPML-NBen_US
dc.subjectVirologyen_US
dc.subjectICP0en_US
dc.titleThe Role of HSV-2 Proteins ICP0 and Us3 in Counteracting Cellular Antiviral Defenceen_US
dc.typeThesisen_US
dc.description.degreeMasteren
dc.contributor.supervisorBanfield, Bruceen
dc.contributor.departmentMicrobiology and Immunologyen


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