Erdmann, VA

Fechner, H

Grunert, HP

Kurreck, J

Poller, W

Rothe, D

Schubert, S

Sipo, I

Werk, D

Zeichhardt, H

English

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Retrovirology
Open AccessPoster presentations
Inhibition of coxsackievirus B3 by RNA interference (RNAi)
J Kurreck1, S Schubert1, D Werk1, D Rothe1, HP Grunert2, I Sipo3, H Fechner3, 
W Poller3, VA Erdmann1 and H Zeichhardt*2
Address: 1Free University Berlin, Institute for Biochemistry, Berlin, Germany, 2Charité CBF, Department Virology, Berlin, Germany and 3Charité 
CBF, Department Cardiology, Berlin, Germany
* Corresponding author    
Here, we demonstrate the potential of RNAi to inhibit a
picornavirus, coxsackievirus B3 (CVB3), a major causes of
myocardial diseases. Targeting the 3D RNA dependent
RNA polymerase (RdRP) with virus specific small interfer-
ing RNAs (siRNAs) resulted in a reduction of the virus titre
by up to 90%. A detailed analysis of the mechanism of
virus silencing with strand-specific siRNAs revealed that
only the viral plus-strand can be efficiently targeted in an
RNAi approach, whereas the minus-strand is resistant to
siRNA-mediated silencing. CVB3 is known to have a high
error-rate during replication and can thus be expected to
escape RNAi-silencing upon prolonged treatment. We
have therefore developed an siRNA double expression
vector (SiDEx), which generates two independent siRNAs
simultaneously. This vector maintained its silencing
capacity against the target RNA with an artificially intro-
duced mutation in a reporter assay, whereas single siRNA-
expression vectors lost their capacity to silence their
respective target after substitution of a base in the centre
of the target site. We will present a recently developed
method to drastically facilitate and accelerate the genera-
tion of SiDEx vectors. Delivery of the siRNA double
expression cassette into neonatal rat cardiomyocytes by an
adenovirus-associated virus vector resulted in up to 370
fold reduction of the CVB3 titre. As an alternative
approach to cope with the problem of viral escape, we
silenced the coxsackievirus-adenovirus receptor on the
host cell and achieved a significant reduction of CVB3
propagation.
from 2006 International Meeting of The Institute of Human Virology
Baltimore, USA. 17–21 November, 2006
Published: 21 December 2006
Retrovirology 2006, 3(Suppl 1):P77 doi:10.1186/1742-4690-3-S1-P77
<supplement> <title> <p>2006 International Meeting of The Institute of Human Virology</p> </title> <note>Meeting abstracts. A single PDF containing all abstracts in this Supplement is available <a href=" http://www.biomedcentral.com/content/files/pdf/1742-4690-3-S1-full.pdf ">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-3-S1-info.pdf</url></supplement>
© 2006 Kurreck et al; licensee BioMed Central Ltd. 


Inhibition of coxsackievirus B3 by RNA interference (RNAi)

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