| dc.contributor.author | Salsman, Jayme Robb Allan. | en_US |
| dc.date.accessioned | 2014-10-21T12:36:43Z | |
| dc.date.available | 2006 | |
| dc.date.issued | 2006 | en_US |
| dc.identifier.other | AAINR19594 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54832 | |
| dc.description | The fusogenic reoviruses are the only examples of non-enveloped viruses that encode membrane fusion proteins. The non-structural fusion-associated small transmembrane (FAST) proteins are the smallest known membrane fusion proteins and are the only viral gene products required to mediate extensive cell-cell fusion and syncytium formation in infected and FAST protein-transfected cells. | en_US |
| dc.description | Analysis of four different FAST proteins (ARV-p10, NBV-p10, BRV-p15 and RRV-p14) in transfected cells revealed that they indirectly alter membrane permeability to small molecules (e.g. uridine and hygromycin B) by producing large syncytia that lose membrane integrity when they die by apoptosis. These observations support a dual role for syncytium formation in the reovirus replication cycle. Fusion at early infection times allows the infection to spread locally and safely access the replication machinery of neighbouring cells. Extensive syncytium formation late in infection leads to apoptosis-induced membrane permeability, facilitating virus release and dissemination of the infection. These results also indicate that the FAST proteins are dedicated cell-cell fusion proteins, but the mechanism of FAST protein-mediated fusion remains unclear. | en_US |
| dc.description | The small size of the FAST proteins, and their lack of structural similarity to other viral fusion proteins, suggest they may mediate fusion through a novel mechanism. The larger viral fusion proteins use complex triggered conformational rearrangements to supply the energy necessary to drive membrane fusion. Analysis of the FAST proteins reveals that they lack specific receptor-binding capability and instead they exploit the closeness provided by cadherin-dependent cellular adhesion machinery to mediate efficient cell-cell fusion. In addition, other cell factors, such as membrane cholesterol and actin remodelling, are critical for FAST protein function, further indicating the importance of the cellular environment in dictating the success of FAST protein-mediated fusion. | en_US |
| dc.description | The FAST proteins are the only fusion proteins that have uncoupled receptor binding from membrane fusion, resulting in an untriggered and unregulated fusion reaction. This unique scenario has allowed the FAST proteins to adopt novel and alternate strategies for mediating membrane merger and as such they offer a new perspective on the process of biological membrane fusion.* | en_US |
| dc.description | *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Windows MediaPlayer or RealPlayer. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2006. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Cell. | en_US |
| dc.subject | Biology, Virology. | en_US |
| dc.title | The reovirus FAST proteins: A new perspective on protein-mediated membrane fusion. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
