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dc.contributor.authorAndersen, Lauren Elizabeth
dc.date.accessioned2014-03-04T20:23:24Z
dc.date.available2014-03-04T20:23:24Z
dc.date.issued2011-12
dc.identifier.otherandersen_lauren_e_201112_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/andersen_lauren_e_201112_phd
dc.identifier.urihttp://hdl.handle.net/10724/27660
dc.description.abstractHuman protein kinases (HPKs) have profound effects on cellular responses. To better understand the role of HPKs and the signaling networks that influence influenza replication, a siRNA screen of 720 HPKs was performed. From the screen, 17 “hit” HPKs (NPR2, MAP3K1, DYRK3, EPHA6, TPK1, PDK2, EXOSC10, NEK8, PLK4, SGK3, NEK3, PANK4, ITPKB, CDC2L5, CALM2, PKN3, and HK2) were validated as important for A/WSN/33 influenza virus replication, and 6 HPKs (CDC2L5, HK2, NEK3, PANK4, PLK4 and SGK3) identified as important for A/New Caledonia/20/99 influenza virus replication. Meta-analysis of the hit HPK genes identified important for influenza virus replication showed a level of overlap, most notably with the p53/DNA damage pathway. In addition, microRNAs (miRNAs) predicted to target the validated HPK genes were determined based on miRNA seed site predictions from computational analysis and then validated using a panel of miRNA agonists and antagonists. The results identify miRNA regulation of hit HPK genes identified, specifically miR-148a by targeting CDC2L5 and miR-181b by targeting SGK3, and suggest these miRNAs also have a role in regulating influenza virus replication. Together these data advance our understanding of miRNA regulation of genes critical for virus replication and are important for development novel influenza intervention strategies.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectInfluenza virus
dc.subjecthost protein kinase
dc.subjectantiviral signaling
dc.subjectRNA interference
dc.subjectRNAi
dc.subjectshort interfering RNA
dc.subjectsiRNA
dc.subjectgenome screen
dc.subjectmicroRNA
dc.subjectmiRNA
dc.titleMiRNA regulation and human protein kinase genes required for influenza virus replication
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentInfectious Diseases
dc.description.majorInfectious Diseases
dc.description.advisorRalph Tripp
dc.description.committeeRalph Tripp
dc.description.committeeR. Jeff Hogan
dc.description.committeeS. Mark Tompkins
dc.description.committeeDavid Suarez
dc.description.committeeZhen Fu


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