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. / October 2007
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.anitoba.ca/dspace#1993/2809 |
| Date | 12 September 2007 |
| Creators | Sawatsky, Bevan |
| Contributors | Czub, Markus (Medical Microbiology), Wylie, John (Medical Microbiology) Leygue, Etienne (Biochemistry and Medical Genetics) Talbot, Pierre (Institut Armand-Frappier) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
| Format | 29095476 bytes, application/pdf |
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