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primary topic: Molecular Studies on Dengue Virus-Host Interaction

Molecular Studies on Dengue Virus-Host Interaction
type: Article
abstract: Dengue is the most prevalent mosquito-borne viral disease world-wide. The causative agent Dengue Virus (DENV) is a positive strand RNA virus replicating predominantly in monocyte-derived macrophages and dendritic cells. The severi-ty of the disease is strongly linked to the level of viral replication, which is de-termined, amongst others by pre-existing DENV-specific antibodies and genetic determinants of the virus and the host. The aim of my thesis was to characterize the role of nonstructural protein 5 (NS5) for the DENV replication cycle. NS5 is a multifunctional protein involved in viral RNA replication, 5’ end capping and blocking of interferon (IFN)-mediated signaling by degrading STAT2. Although DENV replicates in the cytoplasm, NS5 mostly accumulates in the nucleus of infected cells. This study investigated the determinants of NS5 nuclear transport and the effects of nuclear NS5 on viral replication and innate immunity. Nuclear accumulation of NS5 occurred inde-pendent from other viral proteins and was found in infected mammalian and mosquito cells arguing for an evolutionarily conserved property. A mutation analysis was used to identify amino acid residues in NS5 essential for nuclear accumulation. Replication analyses of these nuclear localization signal (NLS) mu-tants showed that even though a high level of nuclear NS5 is not required for efficient DENV replication, complete abrogation of nuclear transport significantly reduced viral replication. Interestingly, the poorly replicating NLS mutants could not be rescued by providing wild type protein in trans indicating that factors other than nuclear NS5 are responsible for their poor replication. To check whether these NLS mutations affect enzymatic activities of NS5, recombinant full length proteins were bacterially expressed and purified. Enzymatic assays showed that save for one, none of the NLS mutations impaired RNA-dependent RNA polymerase or methyl transferase activity. Moreover, IFN sensitivity of t…
date: 2010
status: published
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Molecular Studies on Dengue Virus-Host Interaction (PDF)
has document: Molecular Studies on Dengue Virus-Host Interaction (Other)
subject: 570 Biowissenschaften, Biologie

Molecular Studies on Dengue Virus-Host Interaction (PDF)
type: Document
has file: Anil_Thesis_Final.pdf
has part: Anil_Thesis_Final.pdf

Anil Kumar Victoria Ansalem
type: Person
given name: Anil Kumar
family name: Victoria Ansalem

Molecular Studies on Dengue Virus-Host Interaction (Other)
type: Document
is version of: Molecular Studies on Dengue Virus-Host Interaction (PDF)
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Molecular Studies on Dengue Virus-Host Interaction (Other)
type: Document
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Molecular Studies on Dengue Virus-Host Interaction (Other)
type: Document
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Molecular Studies on Dengue Virus-Host Interaction (Other)
type: Document
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Molecular Studies on Dengue Virus-Host Interaction (Other)
type: Document
is version of: Molecular Studies on Dengue Virus-Host Interaction (PDF)
is volatile version of: Molecular Studies on Dengue Virus-Host Interaction (PDF)
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HTML Summary of #10750 Molecular Studies on Dengue Virus-Host Interaction
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primary topic: Molecular Studies on Dengue Virus-Host Interaction

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en