The role of apoptotic factors in Sindbis virus infection and replication in the mosquito vector Aedes aegypti

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Show simple item record O'Neill, Katelyn Leigh 2013-03-20T13:23:17Z 2013-03-20T13:23:17Z 2013-03-20
dc.description.abstract Mosquitoes are carriers of a variety of harmful human pathogens, including viruses. In order to be successfully transmitted, a virus must evade mosquito immune responses. In this work, the innate immune role of apoptosis in mosquito-virus interactions was examined utilizing the disease vector Aedes aegypti and Sindbis virus. Ae. aegypti is the main vector for yellow fever and dengue virus, which result in over 100 million infections per year. Sindbis virus (Togaviridae) can be transmitted to vertebrates by Ae. aegypti in the laboratory. Sindbis is also well characterized molecularly, making it a good model system for understanding virus-vector interactions. Sindbis MRE-16 recombinant virus clones were utilized to express either an antiapoptotic or pro-apoptotic gene during virus replication. Mosquitoes were infected with recombinant virus clones during a blood meal or by intrathoracic injection. Midgut tissue and whole body samples were analyzed for virus infection and dissemination. Virus was also quantified in saliva and mosquito survival was assayed. Decreased infection in the midgut and delayed virus replication were observed in mosquitoes that were infected with virus expressing a pro-apoptotic gene. Infection with this virus clone also resulted in less virus in the saliva and reduced survival of infected mosquitoes. In addition, negative selection against pro-apoptotic gene expression during virus replication was observed. Collectively, these data suggest that apoptosis can serve as an antiviral defense in Ae. aegypti and may potentially be exploited to control virus transmission. An additional study included in this dissertation focused on zebrafish development and migration of somitic precursors from the tailbud. The tailbud consists of a population of stem cells at the posterior tip of the embryonic tail. The exit of these stem cells from the tailbud is required for the formation of tail somites. A novel double mutant was identified that lacked the t-box transcription factor spadetail and the BMP inhibitor chordin. Double mutants completely lacked somites and had an enlarged tailbud due to accumulation of stem cells that were unable to exit the tailbud. This study indicates the importance of BMP inhibition and spadetail expression in the proper exit of muscle precursors from the tailbud. en_US
dc.description.sponsorship National Institute of Health, Kansas Agricultural Experiment Station, Terry C. Johnson Center for Basic Cancer Research, Kansas IDeA Network of Biomedical Research Excellence program of the National Center for Research Resources en_US
dc.language.iso en_US en_US
dc.publisher Kansas State University en
dc.subject Sindbis en_US
dc.subject Aedes aegypti en_US
dc.subject Apoptosis en_US
dc.subject Zebrafish en_US
dc.subject Tailbud en_US
dc.title The role of apoptotic factors in Sindbis virus infection and replication in the mosquito vector Aedes aegypti en_US
dc.type Dissertation en_US Doctor of Philosophy en_US
dc.description.level Doctoral en_US
dc.description.department Department of Division of Biology en_US
dc.description.advisor Rollie J. Clem en_US
dc.subject.umi Developmental Biology (0758) en_US
dc.subject.umi Molecular Biology (0307) en_US
dc.subject.umi Virology (0720) en_US 2013 en_US May en_US

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