Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography
Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be d...
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| Format: | Online |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547835/ |
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pubmed-35478352013-01-22 Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography Wang, Xue Xu, Fengting Liu, Jiasen Gao, Bingquan Liu, Yanxin Zhai, Yujia Ma, Jun Zhang, Kai Baker, Timothy S. Schulten, Klaus Zheng, Dong Pang, Hai Sun, Fei Research Article Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 Å resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 Å resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ∼5.5 Å, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection. Public Library of Science 2013-01-17 /pmc/articles/PMC3547835/ /pubmed/23341770 http://dx.doi.org/10.1371/journal.ppat.1003132 Text en © 2013 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wang, Xue Xu, Fengting Liu, Jiasen Gao, Bingquan Liu, Yanxin Zhai, Yujia Ma, Jun Zhang, Kai Baker, Timothy S. Schulten, Klaus Zheng, Dong Pang, Hai Sun, Fei |
| spellingShingle |
Wang, Xue Xu, Fengting Liu, Jiasen Gao, Bingquan Liu, Yanxin Zhai, Yujia Ma, Jun Zhang, Kai Baker, Timothy S. Schulten, Klaus Zheng, Dong Pang, Hai Sun, Fei Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| author_facet |
Wang, Xue Xu, Fengting Liu, Jiasen Gao, Bingquan Liu, Yanxin Zhai, Yujia Ma, Jun Zhang, Kai Baker, Timothy S. Schulten, Klaus Zheng, Dong Pang, Hai Sun, Fei |
| author_sort |
Wang, Xue |
| title |
Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| title_short |
Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| title_full |
Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| title_fullStr |
Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| title_full_unstemmed |
Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography |
| title_sort |
atomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography |
| description |
Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 Å resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 Å resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ∼5.5 Å, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547835/ |
| _version_ |
1611947833620955136 |