Our data clearly demonstrate that the purification process affects the integrity of the native quaternary structure of NoV VLPs and, subsequently, the receptor-binding functionality of the VLPs. Although the majority of the VLPs purified by the CsCl method seemed intact in the EM image, the difference from sucrose-density-gradient-purified VLPs in HBGA binding is striking. This result is supported by the recent finding that CsCl has a negative impact on the functionality of VLPs [5] . We also demonstrated that even heat-disrupted VLPs have binding capability, but intact homogenous VLPs have a significantly greater binding intensity. Standardization of the purification method for NoV VLPs used in diagnostic serological assays and blocking assays [8] would greatly strengthen the results obtained.