Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography

Xue Wang, Fengting Xu, Jiasen Liu, Bingquan Gao, Yanxin Liu, Yujia Zhai, Jun Ma, Kai Zhang, Timothy S. Baker, Klaus Schulten, Dong Zheng, Hai Pang, Fei Sun

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere1003132
JournalPLoS pathogens
Volume9
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Wang, X., Xu, F., Liu, J., Gao, B., Liu, Y., Zhai, Y., Ma, J., Zhang, K., Baker, T. S., Schulten, K., Zheng, D., Pang, H., & Sun, F. (2013). Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography. PLoS pathogens, 9(1), [e1003132]. https://doi.org/10.1371/journal.ppat.1003132