Poster abstracts

Poster number 14 submitted by Brandon Michalides

A role for ZNF622 in MAVS signaling

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. 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). A strong RLR and IFN response is essential for controlling viral infections, but its dysregulation can cause tissue damage and contribute to autoimmune diseases. Previous work in the lab identified proteins with altered interaction with MAVS in the presence of RNA and performed small interfering RNA screens to determine if these factors altered IFN induction upon RLR activation. This identified ZNF622 as a potential negative regulator of IFN activation. ZNF622 is a poorly characterized zinc-finger containing RNA-binding protein with reported roles in translation control and stress-induced signaling. We have found that depletion of ZNF622 by siRNA promotes MAVS signaling and IFN induction in response to poly-U/UC RIG-I agonist RNA. This is replicated in studies using ZNF622 KO cells. Additionally, loss of ZNF622 also promotes the expression of antiviral IFN stimulated genes and other innate immune cytokines like IL8. Overall, this work suggests that ZNF622 is a novel regulator of the MAVS signalosome. Currently we are continuing to investigate the molecular mechanisms by which ZNF622 regulates the MAVS signalosome using newly generated knockout, overexpressed, and complimented ZNF622 KO cell lines.

Keywords: ZNF622, Innate Immunity, MAVS