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|Title:||CHARACTERIZATION OF ΔM51-VSV EXPRESSING BECLIN1|
|Authors:||Smith, Elspeth K.|
|Keywords:||autophagy oncolytic viral pathogenesis apoptosis rapamycin VSV;Medical Immunology;Medical Pathology;Medical Immunology|
|Abstract:||<p>Autophagy is a cellular process in which cytoplasmic material is lysosomally degraded into its basic components. The primary functions of this process are cellular recycling and stress mitigation however it also has roles in both viral pathogenesis and tumourigenesis. Beclin1 is a key mediator of autophagy and is involved in its initiation. In an attempt to examine the effects of enhanced autophagy in the context of oncolytic VSV infection, a VSV mutant (ΔM51) expressing Beclin1 was constructed and characterized. It was determined through western blot analysis of autophagy marker LC3, that while VSV infection enhanced autophagy in infected cells, Beclin1 expression resulted in a transient increase in autophagy followed by markedly reduced levels of autophagy at mid to late time points. Still, Beclin1expression, either directly or possibly through altering the kinetics of VSV induced autophagy, enhanced the pathogenesis of VSV<em> </em>in some cell lines <em>in vitro</em>. However examination of the <em>in vivo</em> pathogenesis of VSV-Belcin1 elicited no differences from that of the parental virus. Despite enhanced pathogenesis in CT26 cells <em>in vitro</em>, VSV-Beclin1 displayed no improvement in the oncolysis of CT26 tumours <em>in vivo</em>, compared to VSV-GFP. It is hoped that the conclusions drawn from this study will help direct future research aimed at exploring the relationship between autophagy and VSV pathogenesis as well as future attempts to arm VSV with the intent of augmenting its oncolytic potential.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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