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dc.contributor.advisorBrady, Gareth
dc.contributor.authorPhelan, Thomas
dc.date.accessioned2023-06-20T08:55:41Z
dc.date.available2023-06-20T08:55:41Z
dc.date.issued2023en
dc.date.submitted2023
dc.identifier.citationPhelan, Thomas, Investigating Molluscum Contagiosum Virus Protein MC008 and its Effect on Inflammatory Signalling, Trinity College Dublin.School of Medicine, 2023en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/102972
dc.descriptionAPPROVEDen
dc.description.abstractMolluscum contagiosum virus (MCV) is a human-adapted poxvirus that causes a common, persistent, yet mild infection characterized by distinct, contagious, papular skin lesions. These lesions are notable for having little or no inflammation associated with them and can persist for long periods without an effective clearance response from the host. Like all poxviruses, MCV encodes potent immunosuppressive proteins which perturb innate immune pathways involved in virus sensing, the interferon response and inflammation which collectively orchestrate anti-viral immunity and clearance. Our initial investigation focused on an interaction with the E3 ligase, TRIM32, a protein shown to be involved in cGAS-STING sensing of DNA. This interaction was identified from analysis of MC008 co-purifying proteins by mass spectrometry prior to PhD project commencement. However, we were unable to discern a direct mechanism of MC008 inhibition through this protein. Since several innate immune pathways converge at common signalling nodes, we investigated further downstream. One key node is the regulator of canonical nuclear factor kappa B (NF-κB) activation, NF-κB essential modulator (NEMO). In this thesis, we report that the MCV protein MC008 inhibits NF-κB through its interaction with NEMO, disrupting its early ubiquitin-mediated activation and subsequent downstream signalling. MC008 is the third NEMO-targeting inhibitor to be described in MCV to date, with each inhibiting NEMO activation in distinct ways, highlighting a strong selective pressure to evolve multiple ways of disabling this key signalling protein.en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Medicine. Discipline of Clinical Medicineen
dc.rightsYen
dc.subjectNEMOen
dc.subjectInnate immunityen
dc.subjectMolluscum contagiosumen
dc.subjectMC008en
dc.subjectNF-κBen
dc.titleInvestigating Molluscum Contagiosum Virus Protein MC008 and its Effect on Inflammatory Signallingen
dc.typeThesisen
dc.relation.referencesMolluscum Contagiosum Virus Protein MC008 Targets NF-κB Activation by Inhibiting Ubiquitination of NEMOen
dc.relation.referencesTargeting of the cGAS-STING system by DNA virusesen
dc.relation.referencesDynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacityen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelDoctoralen
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:PHELANTHen
dc.identifier.rssinternalid256602en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorProvost PhD Project Awardsen


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