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Functional characterization of the attachment glycoprotein of Nipah virus: role in fusion, inhibition of henipavirus infection, generation of chimeric proteins, and assembly of chimeric viruses

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dc.contributor.supervisor Czub, Markus (Medical Microbiology) en
dc.contributor.author Sawatsky, Bevan
dc.date.accessioned 2007-09-12T13:14:32Z
dc.date.available 2007-09-12T13:14:32Z
dc.date.issued 2007-09-12T13:14:32Z
dc.identifier.citation Sawatsky, Bevan, Allen Grolla, Nina Kuzenko, Hana Weingartl & Markus Czub (2007). Inhibition of henipavirus infection by Nipah virus attachment glycoprotein occurs without cell-surface downregulation of ephrin-B2 or ephrin-B3. Journal of General Virology 88(2):582-591 en
dc.identifier.uri http://hdl.handle.net/1993/2809
dc.description.abstract Nipah virus (NiV) and Hendra virus (HeV) have been identified as the causes of outbreaks of fatal meningitis, encephalitis, and respiratory disease in Australia, Malaysia, Bangladesh, and India from 1994 until 2004. In order to accommodate the unique genomic characteristics of NiV and HeV, a new genus within the family Paramyxoviridae was created, named Henipavirus. NiV encodes two surface glycoproteins: the attachment glycoprotein (G) binds to the cellular receptor for the virus, while the fusion glycoprotein (F) mediates membrane fusion between the virus and cell membranes. Expression of F and G in the same cell results in cell-cell fusion in transfected cell monolayers, while expression of F and G on their own in cell monolayers does not result in fusion. Co-culture of singly-transfected F and G cells also does not result in fusion. Expression of NiV G in transgenic CRFK cells results in resistance to NiV- and HeV-induced cytopathic effect. Additionally, neither NiV nor HeV nucleic acid could be detected in CRFK-NiV G that had been exposed to NiV or HeV. NiV G expression also prevents NiV F+NiV G-mediated cell-cell fusion, but does not affect cell surface expression of either virus receptor, ephrin-B2 and ephrin-B3. Chimeric glycoproteins derived from NiV G and CDV H were constructed and characterized. None of the chimeric glycoproteins were able to fuse when coexpressed with either NiV F or CDV F. Only one of the chimeric glycoproteins (H145/G458) was detected on the cell surface by immunofluorescence assay (IFA). None of the chimeric glycoproteins altered cell surface expression levels of ephrin-B2 and ephrin-B3. Finally, recombinant NiV genomes (rNiV and rNiV eGFPG) were constructed, as well as chimeric CDV genomes with NiV ORF substitutions (rCDV eGFPH NiVFG and rCDV eGFPH NiVMFG). The only chimeric virus that was generated, rCDV eGFPH NiVFG, was assessed for its release from infected cells. rCDV eGFPH NiVFG was poorly released from infected cells without a freeze-thaw cycle, but was also found to induce the cellsurface down-regulation of the viral receptors ephrin-B2 and ephrin-B3. en
dc.format.extent 29099913 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Nipah virus en
dc.subject attachment glycoprotein en
dc.subject transgenic cells en
dc.subject fusion inhibition en
dc.subject ephrin-B2 en
dc.subject ephrin-B3 en
dc.subject chimeric glycoproteins en
dc.subject chimeric viruses en
dc.subject viral interference en
dc.subject paramyxovirus en
dc.title Functional characterization of the attachment glycoprotein of Nipah virus: role in fusion, inhibition of henipavirus infection, generation of chimeric proteins, and assembly of chimeric viruses en
dc.degree.discipline Medical Microbiology en
dc.contributor.examiningcommittee Wylie, John (Medical Microbiology) Leygue, Etienne (Biochemistry and Medical Genetics) Talbot, Pierre (Institut Armand-Frappier) en
dc.degree.level Doctor of Philosophy (Ph.D.) en
dc.description.note October 2007 en


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