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Investigation of the role of the RNA-dependant RNA polymerase in the transcription and replication of the 1918 pandemic Influenza A virus

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dc.contributor.supervisor Kobasa, Darwyn (Medical Microbiology) en_US
dc.contributor.author Bow, Sarah Jane
dc.date.accessioned 2013-09-16T19:37:52Z
dc.date.available 2013-09-16T19:37:52Z
dc.date.issued 2013-09-16
dc.identifier.uri http://hdl.handle.net/1993/22196
dc.description.abstract The 1918 “Spanish Flu” pandemic was cause by an Influenza A virus that infected 500 million people and nearly 50 million people died. Influenza viruses utilize a RNA-Dependant RNA Polymerase (RdRp) complex, composed of the PA, PB1 and PB2 proteins along with the viral nucleoprotein (NP) to mediate viral transcription and replication. The 1918 PB1 gene has been linked to increased virulence in mice and ferrets. We have investigated the role of PB1 in the transcription and replication of the 1918 virus and its relation to pathogenicity by comparing its RdRp to the RdRp of a low virulence conventional H1N1 human virus isolate, A/Canada/RV733/2007 (RV733). Contrary to previous studies, our dual-luciferase reporter assay revealed the 1918 RdRp had lower transcriptional activity than the RV733 RdRp in vitro. The 1918 NP seems to be the key determinant for the difference in transcriptional activity of the 1918 and RV733 RdRp complexes. The 1918 PB1 in the RV733 RdRp maintained high reporter expression while the RV733 PB1 in the 1918 RdRp abolished reporter expression. 1918/RV733 chimeric PB1 proteins were also generated and evaluated with the reporter assay. Recombinant RV733/1918 viruses were generated by reverse genetics and we determined that PB1 is a key determinant of the high growth phenotype of the 1918 virus, but only a minor contributor to pathogenicity. A novel role for the 1918 NP in the high growth phenotype and pathogenicity of the 1918 virus is also described. en_US
dc.subject Influenza en_US
dc.subject Virology en_US
dc.subject Minigenome en_US
dc.subject Transcription en_US
dc.subject Reverse Genetics en_US
dc.subject Replication en_US
dc.title Investigation of the role of the RNA-dependant RNA polymerase in the transcription and replication of the 1918 pandemic Influenza A virus en_US
dc.degree.discipline Medical Microbiology en_US
dc.contributor.examiningcommittee Ball, Blake T. (Medical Microbiology) Theriault, Steven (Microbiology) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2013 en_US


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