Amino acid substitutions in norovirus VP1 dictate cell tropism via an attachment process dependent on membrane mobility.

All viruses initiate infection by utilising receptors to attach to target host cells. These virus-receptor interactions can therefore dictate viral replication and pathogenesis. Understanding the nature of virus-receptor interactions could also be important to developing novel therapies. Noroviruses are non-enveloped icosahedral viruses of medical importance. They are a common cause of acute gastroenteritis with no approved vaccine or therapy and are a tractable model for studying fundamental virus biology. In this study, we utilise the murine norovirus model system to show that variation in a single amino acid of the major capsid protein can alone can affect viral infectivity through improved attachment to suspension cells. Reducing plasma membrane mobility reduced infectivity, providing an insight into the importance of membrane mobility for receptor recruitment. Furthermore, variation at this site was able to change viral distribution in a murine model, illustrating how in-host capsid evolution can influence viral infectivity and immune evasion.