Poster abstracts
Poster number 105 submitted by Brandon Michalides
Mechanistic characterization of RNA-dependent interactors of the MAVS signalosome
Brandon A. Michalides (Immunobiology, Cincinnati Childrens Hospital Medical Center CCHMC), Janhavi Sahasrabudhe (Immunobiology, Cincinnati Childrens Hospital Medical Center CCHMC), Nandan Gokhale (Immunobiology, Cincinnati Childrens Hospital Medical Center CCHMC)
Abstract:
RIG-I–like receptors (RLR) are critical mediators of antiviral immunity. A strong innate antiviral response is essential for controlling infections, but its dysregulation can cause tissue damage and contribute to autoimmune diseases. Upon sensing of viral RNA, RLRs translocate to contact sites between the endoplasmic reticulum and mitochondria where they interact with the mitochondrial antiviral signaling protein (MAVS). MAVS then oligomerizes and recruits other proteins to form the MAVS signalosome. This signaling platform leads to downstream activation of transcription factors like IRF3 and NF-kB, thereby inducing type I interferons (IFN). Previous work in the lab used mass spectrometry to identify proteins with altered interaction with MAVS in the presence of ribonucleic acid (RNA) and performed small interfering RNA screens to investigate whether IFN induction was altered after RLR activation. Four factors, GPX8, GDI2, RAB13, ZNF622, promoted IFN induction and a maximal antiviral response. We are starting to investigate the molecular mechanisms by which these factors regulate the MAVS signalosome and antiviral signaling using knockout and overexpression models.
Keywords: RIG-I, Innate Immunity, MAVS