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dc.contributor.authorMorazzani, Elaine M.en_US
dc.date.accessioned2014-03-14T21:18:49Z
dc.date.available2014-03-14T21:18:49Z
dc.date.issued2011-08-31en_US
dc.identifier.otheretd-09122011-155411en_US
dc.identifier.urihttp://hdl.handle.net/10919/39328
dc.description.abstractMosquito-borne diseases remain a significant burden on global public health. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although infection of the vertebrate host is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. It is well known that invertebrates rely on small RNA pathways as an adaptive antiviral defense. The canonical antiviral response in these organisms involves dicer enzymes that cleave viral double-stranded RNA replicative intermediates (RIs) into small interfering RNAs (siRNAs; ~21-24 nucleotides). One strand of the siRNA duplex guides the targeting and destruction of complementary viral RNAs when loaded and retained in a multi-protein complex called the RNA-induced silencing complex. Here, we show that mosquito vectors mount a redundant double defense against virus infection mediated by two different small RNA pathways. Specifically, we demonstrate that in addition to a canonical antiviral response mediated by siRNAs, virus infection of the mosquito soma also triggers an antiviral immune pathway directed by ping-pong-dependent PIWI-interacting RNAs (piRNAs; ~24-30 nucleotides). The complexity of mosquito antiviral immunity has important implications for understanding how viruses both induce and modulate RNA-silencing responses in mosquito vectors. In mammals, viral RIs induce a range of relatively nonspecific antiviral responses. However, it remains unclear if viral RIs also trigger RNA silencing in mammals. Mosquito-borne viruses represent an ideal model for addressing this question as their transmission cycles involve alternating replication in mammalian and invertebrate hosts. Although we report identifying a subset of virus-derived small RNAs that appear to be products of RNA silencing in two mammalian cell lines infected with the mosquito-borne chikungunya virus (CHIKV), our studies suggest these small RNAs have little biological relevance in combating virus infections. Thus, while the accumulation of virus-derived siRNAs is essential to the survival of mosquitoes infected with CHIKV, they appear to have little functional significance in mammalian antiviral immunity.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartMorazzani_EM_D_2011.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectAedes albopictusen_US
dc.subjectshort interfering RNAsen_US
dc.subjectpiwi-interacting RNAsen_US
dc.subjectchikungunya virusen_US
dc.subjectantiviral immunityen_US
dc.titleModulation of Alphaviruses by Small RNAsen_US
dc.typeDissertationen_US
dc.contributor.departmentEntomologyen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineEntomologyen_US
dc.contributor.committeechairMyles, Kevin M.en_US
dc.contributor.committeememberAdelman, Zachary N.en_US
dc.contributor.committeememberBloomquist, Jeffrey R.en_US
dc.contributor.committeememberRoberts, Paul Christopheren_US
dc.contributor.committeememberTu, Zhijian Jakeen_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-09122011-155411/en_US
dc.date.sdate2011-09-12en_US
dc.date.rdate2011-09-19
dc.date.adate2011-09-19en_US


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