CIRI seminar: Dr. Christian K. PFALLER
Date / Heure
Date(s) - 13/05/2019
10 h 00 min - 11 h 00 min
Amphi Pasteur, Tour CERVI
Dr. Christian K. PFALLER (Paul-Ehrlich-Institute, Langen, Germany), ” Double-edged sword : ADAR1 controls autoimmunity but weakens the antiviral Response ”
Double-stranded RNA (dsRNA) is one of the most potent pathogen-associated molecular patterns inducing innate immune responses through specific receptors, such as Toll-like receptor 3 (TLR3), retinoic acidinducible gene I (RIG-I), melanoma differentiation associated gene 5 (MDA-5) and the protein kinase R (PKR). While the former three receptors induce the expression of type-I interferons (IFN) the latter causes a cellular stress response including translational arrest, all of which generate an antiviral state. However, cellular transcripts can also form immune-activating dsRNA that, if recognized, induces autoimmune reactions. To avoid this, the host relies on the adenosine deaminase acting on RNA 1 (ADAR1), an interferon-inducible enzyme that binds and edits dsRNA thereby masking it from immune recognition. Mutations in ADAR1 are associated with autoimmune disorders such as Aicardi-Goutières-Syndrome, highlighting its important function. Some RNA viruses have learned to take advantage of ADAR1 to escape innate immunity activation. I will discuss our recent findings on the importance of ADAR1 as an immuneregulatory factor and will present insights into the mechanisms of editing of cellular and viral dsRNA structures. I will highlight the importance of PKR and MDA-5 in immune sensing of self and foreign dsRNA. Using the example of measles virus I will discuss how viruses can take advantage of this mechanism to avoid activation of innate immune responses.
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