Dynamic rotation of the protruding domain enhances the infectivity of norovirus.

Norovirus is the major cause of epidemic nonbacterial gastroenteritis worldwide. Lack of structural information on infection and replication mechanisms hampers the development of effective vaccines and remedies. Here, using cryo-electron microscopy, we show that the capsid structure of murine noroviruses changes in response to aqueous conditions. By twisting the flexible hinge connecting two domains, the protruding (P) domain reversibly rises off the shell (S) domain in solutions of higher pH, but rests on the S domain in solutions of lower pH. Metal ions help to stabilize the resting conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two similar P domain conformations were also found simultaneously in the human norovirus GII.3 capsid, although the mechanism of the conformational change is not yet clear. These results provide new insights into the mechanisms of non-enveloped norovirus transmission that invades host cells, replicates, and sometimes escapes the hosts immune system, through dramatic environmental changes in the gastrointestinal tract. Author summary: The capsid structure of caliciviruses has been reported to be classified into two different types, according to the species and genotype. One is the rising type of P domain conformation as shown in human norovirus GII.10 and rabbit hemorrhagic disease virus (RHDV), where the P domain rises from the S domain surface. The other is the resting type of P domain conformation as shown in human norovirus GI.1, sapovirus and San Miguel sea lion virus (SMSV), where the P domain rests upon the S domain. Here, we demonstrate that the P domain of the murine noroviruses changes reversibly between the rising and resting P domain conformation types in response to aqueous conditions. We also found the similar two P domain conformations in human norovirus GII.3 VLPs at the same time. Our findings provide new insights into the mechanisms of viral infection of caliciviruses. [ABSTRACT FROM AUTHOR]