However, whereas at least two picornavirus 3A Benzethonium Chloride proteins interact with the cellular protein GBF-1 to inhibit COPI vesicle budding, NV p22 instead appears to target COPII vesicles with dependence upon a motif that is absent from picornavirus 3A proteins, suggesting that these two proteins take different approaches to the same ultimate outcome. It therefore appears that, like several picornaviruses, noroviruses encode two proteins, p22 and p48, with redundant functions of antagonizing the secretory pathway. FCV p30, a homologue of p22, lacks an ER export signal and localizes exclusively to the ER when independently expressed. This is in line with the inability of BFA to inhibit FCV replication, as it does several picornaviruses, and further supports the notion that caliciviruses utilize a different architecture of cellular machinery for replication than do picornaviruses. A recent study has shown that MNV is also resistant to the cellular effects of BFA and does not have an effect on gross Golgi morphology. It will therefore be interesting to determine the roles of p22 homologues from MNV and FCV in possible antagonism of ER/Golgi trafficking, as this would shed much light on similarities and differences between animal and human caliciviruses. The biological significance of antagonism of the secretory pathway by p22 Chloroquine Phosphate remains to be understood. This may facilitate viral pathogenesis rather than replication in a manner similar to the effect of the picornavirus 3A proteins that inhibit the immune response to virus-infected cells, ultimately leading to a more pathogenic infection. Future study of the immune response to norovirus infection should consider secretory pathway antagonism by p22, as this protein may be key in deactivating interferon and/or cytokine signaling following infection. Additionally, analysis of the cellular response to NV infection has demonstrated that NV is sensitive to IFN when exogenously added to cells replicating the NV genome; however, NV does not induce the IFN pathway or IRF3 activation in Huh7 cells that support a single round of virus replication. Although p22 may be contributing to a reduction in IFN release from cells, the possibility that p22 has additional inhibitory effects on the IFN pathway remains to be explored. 
Since viruses utilize cellular processes and machinery for replication, understanding the mechanisms by which viruses parasitize the cell will both increase our understanding of these pathways and aid in the design of effective anti-viral countermeasures. The human norovirus nonstructural protein p22 encodes a novel and well-conserved motif that mimics a traditional di-acidic ER export signal. Instead of increasing the rate of protein trafficking in the secretory pathway, as is the normal function of these signals, the ER export signal mimic allows p22 to gain access to the secretory pathway, induce Golgi disassembly and inhibit cellular protein secretion. This is the first instance in which a pathogen has been described to use a motif similar to an ER export signal to ultimately inhibit cellular protein secretion. This motif constitutes a new target for the design of anti-viral drugs against noroviruses, as it is necessary for the antagonistic activity of p22 and is highly conserved in human noroviruses. Practically all cellular processes, including every step in the flow of genetic information from gene expression to protein synthesis and degradation, can be affected by lifestyle and dietary habits. Human disorders and nutrient metabolic responses suggest features whose complexities are defined by interactions among genes, and between genes and environmental stimuli. These interactions are often amplified and modulated through regulatory, protein, metabolic and signaling networks. However, our understanding on the nutrient-related network characteristics and function is still limited. Exploiting roles of nutritional compounds for the rational design of strategies to beneficially manipulate cell functions and/or cell fates is highly restricted by this lack of information.