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INVESTIGATION OF POXVIRUS HOST-RANGE AND GENE EXPRESSION IN MAMMALIAN CELLS.

dc.contributor.advisorMoss, Bernarden_US
dc.contributor.authorMendez Rios, Jorge Daviden_US
dc.date.accessioned2014-06-24T06:09:49Z
dc.date.available2014-06-24T06:09:49Z
dc.date.issued2014en_US
dc.identifier.urihttp://hdl.handle.net/1903/15334
dc.description.abstractMembers of the Poxviridae family have been known as human pathogens for centuries. Their impact in society included several epidemics that decimated the population. In the last few centuries, Smallpox was of great concern that led to the development of our modern vaccines. The systematic study of Poxvirus host-range and immunogenicity provided the knowledge to translate those observations into practice. After the global vaccination campaign by the World Health Organization, Smallpox was the first infectious disease to be eradicated. Nevertheless, diseases such as Monkeypox, Molluscum contagiosum, new bioterrorist threads, and the use of poxviruses as vaccines or vectors provided the necessity to further understand the host-range from a molecular level. Here, we take advantage of the newly developed technologies such as 454 pyrosequencing and RNA-Seq to address previously unresolved questions for the field. First, we were able to identify the Erytrhomelagia-related poxvirus (ERPV) 25 years after its isolation in Hubei, China. Whole-genome sequencing and bioinformatics identified ERPV as an Ectromelia strain closely related to the Ectromelia Naval strain. Second, by using RNA-Seq, the first MOCV in vivo and in vitro transcriptome was generated. New tools have been developed to support future research and for this human pathogen. Finally, deep-sequencing and comparative genomes of several recombinant MVAs (rMVAs) in conjunction with classical virology allowed us to confirm several genes (O1, F5, C17, F11) association to plaque formation in mammalian cell lines. We also provided additional evidence that plaque formation and virus replication can be independent. More importantly, we identified a gene as the first gene outside MVA's deletion that explains its host-restriction. Replacement of this region with a cassette containing that gene derived from a replication-competent virus demonstrated to be sufficient to increase viral yield in all mammalian cell lines tested. Several research and clinical applications can be envisioned derived from this work.en_US
dc.language.isoenen_US
dc.titleINVESTIGATION OF POXVIRUS HOST-RANGE AND GENE EXPRESSION IN MAMMALIAN CELLS.en_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.subject.pqcontrolledVirologyen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pquncontrolledhost-rangeen_US
dc.subject.pquncontrolledMolluscum contagiosumen_US
dc.subject.pquncontrolledMVA vaccineen_US
dc.subject.pquncontrolledPoxvirusen_US
dc.subject.pquncontrolledreplicationen_US
dc.subject.pquncontrolledtranscriptomeen_US


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