The vertebrate innate immune system is a powerful evolutionary conserved mechanism that protects the host against microbial infections, e.g. by viruses. A prime characteristic of this system is the secretion of proteins named type I and type III interferon by vertebrate cells early after infection by a virus. These secreted interferons act as alarm signals and they induce a so-called anti-viral state in cells by binding to receptors on the outside of these cells. One of the first interferon-induced genes that was ever discovered is the Mx gene.
Sixty years after the discovery of the mouse Mx1 gene and the recent structural analyses of some of these proteins, it is still very unclear how the Mx proteins can suppress such a wide variety of viruses. Some reports suggest that the antiviral activity of Mx proteins is modulated by still unknown cellular factor(s). The project aims to elucidate how Mx proteins function as cellular antiviral effectors by identifying Mx-interacting proteins. For this, we will use two innovating state of the art Protein-Protein Interaction (PPIs) techniques. The candidate Mx interactors that we will identify with this proteomics-based approach will subsequently be validated functionally. The newly identified Mx-interacting proteins are expected to shed light on how these enigmatic antiviral effector proteins function.