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Influence of Cell Cycle Alteration on Venezuelan Equine Encephalitis Virus

Show simple item record Fontenot, Jacque L 2014-09-15T20:15:14Z 2014-09-15T20:15:14Z 2014-04-29
dc.description.abstract Venezuelan Equine Encephalitis Virus (VEEV), of the Togaviridae family and Alphavirus genus, is the causative agent of potentially fatal viral encephalitis. The virus is transmitted to humans via the bite of infected Culex mosquitoes that have fed on infected equines. VEEV is an emerging pathogen and with no tangible large scale vaccine available, has the potential to cause epidemics. The virally encoded capsid protein is responsible for causing cytopathic effect at least partially due to inducing a transcriptional shutoff in infected cells. A nuclear localization sequence within the capsid protein allows nuclear import of capsid and blocking of the nuclear pores thereby inhibiting the import and export of cellular proteins. Other nuclear localized viral proteins are known to induce alterations of the cell cycle in order to create favorable conditions for viral replication. Understanding how VEEV manipulates the cell cycle will provide possible intracellular targets for future antiviral strategies. In this study we show that VEEV infected cells have a delayed cell cycle progression following serum starvation. Western blot analysis showed decreased Cyclin E and A2 levels at 16 and 24 hours post infection (hpi). Phosphorylation of Rb remained low at 16 and 24hpi in infected cells, further confirming the cell cycle delay in infected cells. UV inactivated VEEV did not induce this delay in return to cell cycle, indicating that replication competent VEEV is needed for the induction of this delay. Cdk4/6 and Cdk1 inhibitor treated cells showed significant decreases in VEEV replication. Hydroxyurea, nocodazole and thymidine synchronized cells showed significant decreases in viral replication as well. The results of our study show that VEEV is delaying the cell cycle progression of synchronized cells and that VEEV needs an actively replicating population of cells for optimal viral replication kinetics. Future studies will focus on confirming that capsid’s nuclear localization is responsible for these observations through the use of a capsid NLS mutant virus.
dc.language.iso en en_US
dc.subject Venezuelan Equine Encephalitis Virus en_US
dc.subject cell cycle en_US
dc.subject capsid en_US
dc.subject cyclin en_US
dc.title Influence of Cell Cycle Alteration on Venezuelan Equine Encephalitis Virus en_US
dc.type Thesis en

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