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The role of Ran-binding protein 3 during influenza A virus replication

dc.contributor.advisorZhou, Yanen_US
dc.contributor.committeeMembervan den Hurk, Sylviaen_US
dc.contributor.committeeMemberTikoo, Sureshen_US
dc.contributor.committeeMemberYang, Jianen_US
dc.creatorPredicala, Reyen_US
dc.date.accessioned2014-06-28T12:00:16Z
dc.date.available2014-06-28T12:00:16Z
dc.date.created2014-04en_US
dc.date.issued2014-06-27en_US
dc.date.submittedApril 2014en_US
dc.description.abstractInfluenza A virus (family Orthomyxoviridae) is one of the most important human pathogens, causing annual epidemics with significant worldwide mortality, and sporadic but potentially devastating pandemics. The influenza A viral genome encodes 14 proteins and consists of 8 segments of negative-stranded RNA. During infection, the virus exploits the host cell signaling machinery to ensure efficient replication. The PI3K/Akt and Ras/ERK are two of the signaling cascades that are induced for virus survival. Influenza A virus replicates in the nucleus, hence the newly synthesized RNPs must be exported from the nucleus and exported to the cell membrane. Although the detailed mechanism of vRNP nuclear export is not yet fully elucidated, several studies on this process have begun to emerge. Influenza A virus nucleoprotein nuclear export is CRM1-dependent. Ran-binding protein 3 (RanBP3) is a Ran-interacting protein that is best known for its role as a cofactor of CRM1-mediated cargo nuclear export. In this study, we investigated the role of RanBP3 during the influenza A virus life cycle. We found that RanBP3 was phosphorylated at Ser58 in early and late phases of infection. Knockdown of RanBP3 expression led to a vRNP nuclear retention, suggesting that RanBP3 is involved in vRNP nuclear export. Moreover, we demonstrated that RanBP3’s function during vRNP nuclear export is regulated by phosphorylation at Ser58, and the RanBP3 phosphorylation is modulated by both PI3K/Akt and Ras/ERK/RSK pathways in the late phase of viral infection. In conclusion, this study has shown that RanBP3 is a host factor that has a vital role during the late stage of influenza A virus replication, specifically as a co-factor in CRM1-mediated nuclear export. Identifying this host factor will contribute to the understanding of the mechanism of vRNP transport.en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2014-04-1526en_US
dc.language.isoengen_US
dc.subjectinfluenza A virusen_US
dc.subjectRanBP3 proteinen_US
dc.subjectnucleocytoplasmic transporten_US
dc.titleThe role of Ran-binding protein 3 during influenza A virus replicationen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentSchool of Public Healthen_US
thesis.degree.disciplineVaccinology and Immunotherapeuticsen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US

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