Rabies-Virus-Infektion der Maus: Einfluss des viralen Glykoproteins auf die Immunantwort im ZNS.
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Philipps-Universität Marburg
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Abstract
The rabies virus glycoprotein (RV-G) plays a central role in the pathogenesis of rabies by determining the neuroinvasiveness and by modulating antiviral immune responses. The mechanism by which RV-G determines the pathogenicity once the virus has reached the brain is still unknown. To study the role of RV-G in the CNS, we infected mice intranasally with the attenuated rabies virus variant SPBN or with the recombinant RV variant SPBN-DOG4. In SPBN-DOG4, the RV-G gene sequence of SPBN was replaced by that of the highly pathogenic street virus strain DOG4. Intramuscular inoculation resulted in 30% mortality in SPBN-DOG4-infected but not in SPBN-infected mice whereas intranasal inoculation of both RV variants resulted in 100% mortality. The mean time of survival was significantly lower in SPBN-infected mice as compared to those infected with SPBN-DOG4. These findings indicate a higher pathogenicity of the SPBN virus strain. Significantly lower virus neutralizing antibody serum titers and IL-6 mRNA levels in the brain and reduced glial activation paralleled the reduced mean time of survival of SPBN-infected animals. Additionally, a correlation with lower virus titers, reduced levels of RV-G and ribonucleoprotein expression in whole brain homogenates could be found. However, on the level of single infected neurons the amount of RV-G was higher in SPBN-infected mice. These data suggest that higher RV-G expression levels in individual infected neurons rather than the overall number of infected neurons defines the pathogenicity of a rabies virus strain. By limiting the cellular RV-G-expression in the brain, new therapeutical concepts in treatment of rabies virus infection could be developed.
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Dates
Created: 2010Issued: 2010-12-29Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
VirusGlycoproteinNeuroimmunologyRabiesVirusRabiesGlycoproteinNeuroimmunologie
DFG-subjects
ZentralnervensystemTollwutGliaImmunsystemImmunreaktion
DDC-Numbers
610
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Krieger, Tilman (143064290): Rabies-Virus-Infektion der Maus: Einfluss des viralen Glykoproteins auf die Immunantwort im ZNS.. : Philipps-Universität Marburg 2010-12-29. DOI: https://doi.org/10.17192/z2010.0714.
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This item has been published with the following license: In Copyright