Untersuchung differentieller Genexpression in Arenavirus-infizierten Zellen und Entwicklung einer therapeutischen siRNA gegen Arenaviren
File | Description | Size | Format | |
---|---|---|---|---|
00010710.pdf | 3.99 MB | Adobe PDF | View/Open |
Other Titles: | Gene Expression profiling and therapeutic siRNA approach for Arenavirus infection | Authors: | Müller, Stefanie | Supervisor: | Dotzauer, Andreas | 1. Expert: | Dotzauer, Andreas | Experts: | Günther, Stephan | Abstract: | The pathogenesis of Lassa virus is poorly understood. Cellular mRNA levels in Lassa virus- and LCMV-infected HuH-7 cells were measured at the late phase of acute infection with two types of transcription array. Data analysis was based on statistical frameworks controlling the false-discovery rate. Data were considered relevant if they could be verified by both array systems and real-time RT-RCR. According to these criteria, there was no evidence for true changes in gene expression. Additionally the ability of siRNA as a therapeutic option in Lassa fever treatment was tested. Therefore conserved sequences of the Lassa virus genome were chosen as siRNA targets. Testing was performed using a Lassa virus minireplicon system and plasmids for CMV promoter-driven expression of Lassa virus mRNA analogues. The siRNA targeting the 5' end of NP mRNA led to 60-80% reduction of reporter gene activity (Renilla luciferase) in both systems. Vero cells transfected with NP-specific siRNA showed 60-90% reduction of infectious virus titre for the Lassa virus strains (NL, LIB-90, AV, CSF, NIG-10) and related arenaviruses (LCMV WE, LCMV Armstrong, Mopeia) included in the studies. |
Keywords: | Arenavirus; gene expression profiling; transcription array; siRNA | Issue Date: | 2-Feb-2007 | Type: | Dissertation | Secondary publication: | no | URN: | urn:nbn:de:gbv:46-diss000107108 | Institution: | Universität Bremen | Faculty: | Fachbereich 02: Biologie/Chemie (FB 02) |
Appears in Collections: | Dissertationen |
Page view(s)
211
checked on Mar 15, 2025
Download(s)
87
checked on Mar 15, 2025
Google ScholarTM
Check
Items in Media are protected by copyright, with all rights reserved, unless otherwise indicated.