Japan Agency for Medical Research and Development (AMED)
JP18fk0108034h0602
日本
Ministry of Education, Culture, Sports, Science and Technology (Japan)
JP26102545
日本
Japan Agency for Medical Research and Development (AMED)
JP18am0101072j0001
日本
Ministry of Education, Culture, Sports, Science and Technology (Japan)
JP16H00786
日本
引用
ジャーナル: PLoS Pathog / 年: 2020 タイトル: Dynamic rotation of the protruding domain enhances the infectivity of norovirus. 著者: Chihong Song / Reiko Takai-Todaka / Motohiro Miki / Kei Haga / Akira Fujimoto / Ryoka Ishiyama / Kazuki Oikawa / Masaru Yokoyama / Naoyuki Miyazaki / Kenji Iwasaki / Kosuke Murakami / ...著者: Chihong Song / Reiko Takai-Todaka / Motohiro Miki / Kei Haga / Akira Fujimoto / Ryoka Ishiyama / Kazuki Oikawa / Masaru Yokoyama / Naoyuki Miyazaki / Kenji Iwasaki / Kosuke Murakami / Kazuhiko Katayama / Kazuyoshi Murata / 要旨: 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 ...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.