Capsid Properties Contributing to Norovirus Persistence in Humans

Human noroviruses (NoVs) are the leading cause of acute gastroenteritis in adults and contribute to an estimated 30-50% of all foodborne illnesses in the United States. They are listed on the US EPA's drinking water contaminant list and have been detected in environmental waters. No routine cell culture or small animal model is yet available, so there are limited options for testing the efficacy of prevention and control strategies. Recently, several areas of research have provided us with new tools for addressing important questions about the fate of NoV outside the human host. In this study, we examined the role of unique properties of the viral capsid protein involved in histo-blood group antigen (HBGA) receptor binding and the stability of the virus in the environment to better understand NoV persistence in human populations. Using a novel murine norovirus surrogate, we determined that NoVs are likely stable at extremes of pH, after treatment with organic solvents, and after incubation at ambient and refrigerated temperatures, but are inactivated at high temperatures. Exploiting human NoV binding to HBGA receptors, we demonstrated that potentially infectious virus can be concentrated and recovered from environmental waters. Finally, using a surrogate neutralization assay, we compared differences in the ability of human NoV outbreak convalescent patient sera collected over a 21 year period to block NoV virus-like particle (VLP) binding to HBGAs. Our results suggest that outbreak patient sera supports antigenic drift of genogroup II, genocluster 4 NoVs in the face of herd immunity. Taken together, the results of this study will enable researchers with novel tools for evaluating the efficacy of prevention and control strategies for human NoVs.