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|Title: ||Role of Calsyntenin-1 in Hepatitis C Virus Pathogenesis|
|Authors: ||Awan, Zunaira|
|Issue Date: ||7-Apr-2015|
|Publisher: ||University of Sydney|
Sydney Medical School
|Abstract: ||Approximately 150 million people worldwide have chronic HCV infection that can lead to hepatic fibrosis, liver failure and cancer. In a proteomic screen of the “secretome” from HCV infected hepatic cells we observed increased (43 fold) secretion of calsyntenin-1, compared to uninfected controls. Calsyntenin-1 is an adapter molecule that links microtubule associated molecular motor kinesin 1 to vesicular cargo in neurons. We showed that calsyntenin-1 is involved in early stages of the viral replication cycle, namely uptake into early endosomes while its loss altered early endosomal distribution, velocities and function. It was also found to be required for the establishment of new HCV replication complexes, their transport and distribution within cell. Furthermore, siRNA-mediated knockdown of calsyntenin-1 showed its association with intracellular trafficking of multivesicular bodies and recycling endosomes by affecting their distribution within HCV infected cells and also reduced exosome infectivity as determined by Deltavision microscopy and infectivity assay (TCID50) analysis. Our results suggest that calsyntenin-1 in involved in multiple stages of HCV replication cycle as an important host factor. The uptake of viral particles into early endosomes, trafficking of replication complexes and egress of virus containing exosomes involve kinesin-1 based transport dependent on membrane adaptor qualities of calsyntenin-1.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
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|AWAN Zunaira - Final Thesis.pdf||Thesis||6.67 MB||Adobe PDF|
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