Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography
| Autor: | Hai-Liang Pang, Yujia Zhai, Jiasen Liu, Klaus Schulten, Dong Zheng, Timothy S. Baker, Yanxin Liu, Fengting Xu, Kai-Ming Zhang, Jun Ma, Bingquan Gao, Fei Sun, Xue-Cong Wang |
|---|---|
| Přispěvatelé: | Saphire, Erica Ollmann |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Hemorrhagic Disease Virus Rabbit Cryo-electron microscopy Rabbit Crystallography X-Ray medicine.disease_cause 01 natural sciences Epitope Protein structure Models Hemorrhagic Disease Virus lcsh:QH301-705.5 Caliciviridae Infections 0303 health sciences Crystallography biology 030302 biochemistry & molecular biology 3. Good health Lagovirus Infectious Diseases Capsid Medical Microbiology Rabbits Infection Research Article Protein Binding Biotechnology lcsh:Immunologic diseases. Allergy Protein Structure Viral protein Immunology Biophysics Viral Structure 010402 general chemistry Microbiology Virus Vaccine Related 03 medical and health sciences Rare Diseases Virology Viral Core Genetics medicine Animals Amino Acid Sequence Biology Molecular Biology 030304 developmental biology Viral Structural Proteins Cryoelectron Microscopy Molecular biology.organism_classification Molecular biology Protein Structure Tertiary 0104 chemical sciences lcsh:Biology (General) X-Ray Parasitology Capsid Proteins Immunization lcsh:RC581-607 Digestive Diseases Sequence Alignment Tertiary |
| Zdroj: | PLoS pathogens, vol 9, iss 1 PLoS Pathogens, Vol 9, Iss 1, p e1003132 (2013) PLoS Pathogens |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2012.11.2307 |
| Popis: | 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. Author Summary Rabbit hemorrhagic disease (RHD), first described in China in 1984, causes hemorrhagic necrosis of the liver within three days after infection and with a mortality rate that exceeds 90%. RHD has spread to large parts of the world and threatens the rabbit industry and related ecology. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. Currently, the absence of a high-resolution model of any lagovirus impedes our understanding of its molecular interactions with hosts and successful design of an efficient anti-RHDV vaccine. Here, we use hybrid structural approaches to construct a pseudo-atomic model of RHDV that reveals significant differences in the P2 sub-domain of the major capsid protein compared to that seen in other caliciviruses. We identified seven regions of high sequence variation in this sub-domain that dictate the binding specificities of histo-blood group antigens. In one of these regions, we identified an antigenic peptide that interacts with rabbit tissue cells and elicits a significant immune response in rabbits and, hence, protects them from RHDV infection. Our pseudo-atomic model provides a structural framework for developing new anti-RHDV vaccines and will also help guide use of the RHDV capsid as a vehicle to display human tumor antigens as part of anti-tumor therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|