Human Noroviruses are single stranded RNA (ssRNA) viruses and the major cause of non-bacterial gastroenteritis worldwide. Due to the lack of a small animal or tissue culture model for Human Noroviruses, aspects of norovirus replication and immune recognition are so far poorly understood. With the discovery of the Murine Norovirus (MNV) and the introduction of an effective model for norovirus infection and replication, knowledge about infection mechanisms and its impact on the host immune response has progressed. MNV infection has been shown to lead to major changes in the microtubule network of infected macrophages causing the formation of thick microtubule bundles. GEF-H1, a guanine nucleotide exchange factor, is associated with microtubules and is activated upon changes in the microtubule network. GEF-H1 interacts with small GTPases including RhoA and RhoB, regulating vesicle trafficking, transcription and the cytoskeleton. Additionally, activated GEF-H1 contributes to our innate immune response by sensing RNA viruses and promoting IFN-β expression. In this study we have observed that GEF-H1 contributes to MNV replication. Upon infection, we observed that GEF-H1 co-localised with the MNV replication complex proximal to the microtubule organising centre. Overexpression of GEF-H1 from a cDNA expression plasmid induced bundling of microtubules analogous to that observed during infection with MNV. Additionally, we observed that expressed GEF-H1 interacted with the viral non-structural protein NS3, leading to an altered distribution of both proteins within the cell. We also showed that overexpression of GEF-H1 during MNV infection leads to the dispersion of the MNV RC indicating that GEF-H1 and microtubules provide a framework for RC biogenesis. Our current research is investigating the role and impact of GEF-H1 in sensing MNV replication in cells.