Investigation of the deregulated miRNome identified during acute viral infections in a murine model of HSV-1 encephalitis

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dc.contributor.supervisor Booth, Stephanie (Medical Microbiology) en_US
dc.contributor.author Caligiuri, Kyle
dc.date.accessioned 2014-09-02T16:32:47Z
dc.date.available 2014-09-02T16:32:47Z
dc.date.issued 2013 en_US
dc.identifier.citation Ying, S.-Y. & Walker, J.M. MicroRNA Protocols. Life Sci. 531, 375 (Humana Press, 2013) en_US
dc.identifier.uri http://hdl.handle.net/1993/23926
dc.description.abstract Herpes simplex virus type 1 (HSV-1) is a double stranded DNA virus that causes epithelial skin infections and persists through the life of the host by infecting neurons, where it can switch to a latent state to evade an immune response. In rare cases during primary infection or after reactivation, instead of undergoing lytic infection at the epithelial surface, it instead travels to the brain and causes herpes simplex virus encephalitis (HSVE) which can have a ≥70% mortality rate if untreated. As the virus takes over its host cell, it gains control of the host cell machinery and manipulates host gene expression in order to evade the immune system and to pool its resources into the replication of the virus. One aspect of the dysregulated gene expression involves microRNAs (miRNAs). MiRNAs are short, non-coding RNAs that bind to the 3' untranslated region (3'UTR) of messenger RNAs (mRNAs), leading to translational repression of the target. Dysregulated miRNAs are often down-regulated during infection as the virus takes over, but many miRNAs have also been found to be up-regulated as well1–5. The aim of this study is to observe the full cellular miRNA changes in the context of an acute viral encephalitic infection using HSV-1, and to further characterize selected up-regulated miRNAs to determine their function in the context of the disease state. Of particular note were miR-141 and miR-200c which showed anti-apoptotic effects on neuronal cell culture and did not impact cell viability during an over-expression of the miRNAs. MiR-141, miR-183 and miR-200a expression was enriched within specific areas of the brain during infection. In addition, the potential for miR-150 to bind to a bioinformatically predicted target site within the shared 3'UTR of the HSV-1 UL18, UL19 and UL20 genes was explored. Examining the changes in expression of this class of regulatory RNAs and investigating their potential functions may yield new insight into the relationship between host and virus during infection. en_US
dc.publisher Springer Science+Business Media, LLC en_US
dc.subject herpes simplex virus type 1 en_US
dc.subject microRNA en_US
dc.subject HSV-1 en_US
dc.subject miRNA en_US
dc.subject next generation sequencing en_US
dc.subject NGS en_US
dc.subject deep sequencing en_US
dc.subject miRNome en_US
dc.subject herpes simplex virus encephalitis en_US
dc.subject HSVE en_US
dc.title Investigation of the deregulated miRNome identified during acute viral infections in a murine model of HSV-1 encephalitis en_US
dc.degree.discipline Medical Microbiology en_US
dc.contributor.examiningcommittee Yao, Xiaojian (Medical Microbiology) Hombach-Klonisch, Sabine (Human Anatomy & Cell Science) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2014 en_US

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