Guest Lecture by Dr. Saurabh Chattopadhyay
Title :
Dual Roles of IRF-3 in Antiviral Defense
Date : 21.08.2013
Time : 4:30 pm
Venue : Lecture Hall II (J. C. Bose Building)
ABSTRACT
IRF-3 is a member of IRF family of transcription factors. Virus infection
activates the latent transcription factor IRF-3 causing its nuclear
translocation and the induction of antiviral genes including interferons.
We have identified that HDAC6 is required for the transcriptional activity
of IRF-3. Our results indicate that the HDAC6-mediated effect on the
transcriptional activity of IRF-3 is via deacetylation of β-catenin,
which enables the recruitment of transcriptional co-activators. In
addition to transcription of antiviral genes, IRF-3 activated by
cytoplasmic RIG-I signaling pathway can efficiently trigger cellular
apoptosis. Using appropriate mutants of IRF-3, we demonstrated that the
apoptotic activity was independent of its transcriptional activity.
Apoptosis was triggered by the interaction of IRF-3 with the pro-apoptotic
protein BAX via a BH3-like domain of IRF-3, their co-translocation to the
mitochondria and the resulting activation of the mitochondrial apoptotic
pathway. Selective ablation of IRF-3 functions significantly augmented
virus replication and pathogenesis. The presentation will highlight how
IRF-3 functions in the two distinct pathways and contributes to the
overall host antiviral response Inflatable Pools.
activates the latent transcription factor IRF-3 causing its nuclear
translocation and the induction of antiviral genes including interferons.
We have identified that HDAC6 is required for the transcriptional activity
of IRF-3. Our results indicate that the HDAC6-mediated effect on the
transcriptional activity of IRF-3 is via deacetylation of β-catenin,
which enables the recruitment of transcriptional co-activators. In
addition to transcription of antiviral genes, IRF-3 activated by
cytoplasmic RIG-I signaling pathway can efficiently trigger cellular
apoptosis. Using appropriate mutants of IRF-3, we demonstrated that the
apoptotic activity was independent of its transcriptional activity.
Apoptosis was triggered by the interaction of IRF-3 with the pro-apoptotic
protein BAX via a BH3-like domain of IRF-3, their co-translocation to the
mitochondria and the resulting activation of the mitochondrial apoptotic
pathway. Selective ablation of IRF-3 functions significantly augmented
virus replication and pathogenesis. The presentation will highlight how
IRF-3 functions in the two distinct pathways and contributes to the
overall host antiviral response Inflatable Pools.
Speaker : Dr. Saurabh Chattopadhyay
Project Staff Scientist,
Dept. of Molecular Genetics,
The Lerner Research Institute,
Cleveland Clinic, Cleveland, Ohio, USA