Maintenance of cellular homeostasis is directly dependent on the proper functioning of the Golgi apparatus, which is central to lipid trafficking and protein secretion. Protein trafficking from the endoplasmic reticulum to the Golgi is mediated by vesicles coated in COPIIproteincomplexes, whereas theretrogradeGolgi-toER pathway is mediated by COPI-coated vesicles. Upon export from the ERat ER exit sites, cellular proteins accumulate and traffic into budding COPII vesicles, which are minimally composed of the GTPase Sar1 and heteromeric complexes of Sec13/31 and Sec23/24. COPII vesicles then traffic along microtubules through the ER/Golgi intermediate compartment to the cis Golgi, where vesicles lose their COPII coat, fuse with the Golgi, and progress to the trans Golgi. A subset of cellular and viral proteins that rapidly exit the ER employ either di-hydrophobic, di-basic or di-acidic ER export signals that mediate their specific uptake into COPII vesicles by direct interaction with either Sec24 or Sar1 at ERES. Export of proteins from the ER and subsequent trafficking of COPII vesicles to the Golgi is mediated by a number of cellular factors, and proteins of both cellular and microbial origin are known to antagonize this pathway. Perhaps the most well-known ER/Golgi trafficking antagonist, the fungal metabolite brefeldin A targets the GTPase ADPribosylation factor 1 responsible for COPI vesicle budding at the Golgi by stabilizing an Arf/Sec7 intermediate during nucleotide exchange. This prevents nucleotide dissociation and ultimately deactivates Arf1 to induce a global inhibition of cellular protein secretion. The 3A proteins encoded by the picornaviruses coxsackievirus B3 and poliovirus also target Arf1. 3A inhibits GBF1, a guanine exchange factor necessary for Arf1 activition, resulting in Golgi disruption and inhibition of protein secretion. Consequently, surface expression of MHC Class I decreases and the normal cytokine release that aids in clearance of infected cells is inhibited. This LOUREIRIN-B results in a prolonged period of viral replication before the infected cell can be cleared by the immune system. Human noroviruses are the causative agent of approximately 23 million annual cases of gastroenteritis in the U.S. and are classified as Category B biodefense pathogens. Noroviruses are composed of five genogroups within the family Caliciviridae, and viruses in genogroups I and II are the most frequently detected in Tulathromycin B humans. Noroviruses code for six nonstructural and two structural proteins; however, one of these proteins, the nonstructural protein p22, has no identified function in any calicivirus, although an early study on the immune response following infection with Norwalk virus, the prototype human norovirus and calicivirus, demonstrated an immune response directed against p22 in convalescent sera. The study of p22 and other human norovirus proteins is complicated by the lack of both an efficient tissue culture system to grow noroviruses and a reverse genetics system to directly examine protein function during viral infection. Replication of two cultivatable animal caliciviruses, feline calicivirus and murine norovirus, induces cellular membrane rearrangements as well as alterations in Golgi architecture, suggesting that Golgi 
disassembly may be a common consequence of infection. In support of this, FCV p30, a homologue of NV p22, is membrane associated and independently induces ultrastructural changes in several secretory pathway organelles, thus proposing ER-derived membranes as a source of membranes to anchor viral genome replication. Similarly, Fernandez-Vega and colleagues demonstrated that the NV nonstructural protein p48 induces Golgi disassembly; however, the possibility of additional viral proteins contributing to alterations in Golgi phenotype and antagonism of protein secretion, as is the case for several picornaviruses, has not been examined. In the current study, we asked if the Golgi rearrangements observed during animal calicivirus and picornavirus replication also occur during human norovirus replication, and if p22 has a role in this process.