Abstract
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.
Highlights
Human norovirus (HNoV) is a major cause of epidemic nonbacterial gastroenteritis worldwide [1]
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 first, called here the rising conformation, is shown in Murine norovirus (MNoV)-1 [12], HNoV GII.10 [13], and rabbit hemorrhagic disease virus (RHDV) [14, 15], where the P domain rises from the S domain surface, forming an outer second shell
Summary
Human norovirus (HNoV) is a major cause of epidemic nonbacterial gastroenteritis worldwide [1]. HNoV often causes severe sporadic infections, especially in nurseries and nursing homes. Murine norovirus (MNoV), a species of norovirus affecting mice, was identified in 2003 [3]. MNoV is a unique norovirus which propagates in cell lines [3, 4], and shares genetic features with HNoV and has biochemically similar properties [5]. For these reasons, MNoV has been widely used as a model for HNoV infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
