RT Journal Article
SR Electronic
T1 Dynamic rotation of the protruding domain enhances the infectivity of norovirus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.16.878785
DO 10.1101/2019.12.16.878785
A1 Chihong Song
A1 Reiko Takai-Todaka
A1 Motohiro Miki
A1 Kei Haga
A1 Akira Fujimoto
A1 Ryoka Ishiyama
A1 Kazuki Oikawa
A1 Masaru Yokoyama
A1 Naoyuki Miyazaki
A1 Kenji Iwasaki
A1 Kosuke Murakami
A1 Kazuhiko Katayama
A1 Kazuyoshi Murata
YR 2019
UL http://biorxiv.org/content/early/2019/12/17/2019.12.16.878785.abstract
AB 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 latter conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two P domain conformations were also found in the human norovirus GII.3 capsid. These results provide new insights into the infection mechanisms of the non-envelope viruses that function in dramatic environmental changes such as the digestive tract.Significance Statement The capsid structures of caliciviruses have been reported to be classified into two different types, according to species and genotype. One is the rising P domain type as shown in human norovirus GII.10 and rabbit hemorrhagic disease virus, where the P domain rises from the S domain surface. The other is the resting P domain type as shown in human norovirus GI.1, sapovirus and San Miguel sea lion virus, where the P domain rests upon the S domain. Here, we demonstrate that the P domain of the murine norovirus infectious particles changes reversibly between the rising and resting P domain types in response to aqueous conditions. Our findings provide new insights into the mechanisms of viral infection of caliciviruses.