Human Noroviruses are highly infectious, single stranded RNA (ssRNA) viruses and the major cause of non-bacterial gastroenteritis worldwide. Despite recent advances in the field, a small animal or efficient tissue culture model for Human Noroviruses still remains to be established. 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. We have recently discovered that MNV inhibits important effectors of the innate immune response, critical in controlling viral replication and systemic spread. A major player in the immune response against viral infections is the group of major histocompatibility complex class I proteins. We have observed that MNV interferes with the antigen presentation pathway in infected cells by reducing the surface expression of MHC class I proteins. We have shown that MNV infected DCs as well as macrophages have a reduced surface expression of MHC class I proteins compared to uninfected and bystander cells. Transcriptional analysis revealed that this defect is not due to decreased amount of mRNA, but is reflected at the protein level. Treatment with the proteasome inhibitor MG132 partly restored the surface expression of MHC class I, indicating a role of the proteasome and degradation of the protein. Additionally, we identified MNV NS3 as the viral protein responsible for the decrease in MHC class I surface expression. Our results indicate that MNV reduces the surface expression of MHC class I proteins to presumably decrease the amount of antigens presented to CD8+ T cells and thus allow the virus to dampen the immune response.