Stephanie Rattay

Identification and Characterization of MCMV-encoded
IFN Antagonists

To counteract the interferon (IFN)-induced antiviral state, MCMV has evolved mechanisms promoting viral replication. Our group showed that the induction of IFN-beta and IFN-alpha-4 transcription is inhibited in MCMV-infected fibroblasts by blocking the signaling pathways inducing the IFN-beta enhanceosome i.e. the activation of IRF3, NF-kappa-B and ATF-2/c-Jun (Le VTK et al. J. Gen. Virol. 2008).
The aim of this study is to identify MCMV-encoded antagonists of IFN-beta transcription. To this end, we first started to examine MCMV gene deletion mutants and monitored the abundance of IFN-beta and IFN-alpha-4 transcripts after infection (“loss of function approach”). In summary, we could exclude approx. 60% of all non-essential MCMV genes to be required for the inhibition of IFN-beta induction. The analysis of the remaining genes with corresponding gene deletion mutants is not possible because the genes are either essential for replication or the deletion results in a severe attenuation of virus growth. Hence, we set out to establish a gain of function approach and to generate an MCMV cDNA library. In order to detect the ORFs responsible for the inhibition of IFN-beta transcription we are currently establishing an IRF-3 and IFN-dependent screening system positively selecting for cells harboring IFN-beta antagonists.

1st supervisor: Prof. Dr. Hartmut Hengel
2nd supervisor: Dr. Khanh Le

Institute:
Department of Virology, Heinrich Heine University Düsseldorf

Telephone: +49 (0)211 - 81 - 10552
E-mail: stephanie.rattay@uni-duesseldorf.de