3j1p Citations

Atomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography.

OpenAccess logo PLoS Pathog. 9 e1003132 (2013)
Related entries: 4egt, 4ejr

Cited: 25 times
EuropePMC logo PMID: 23341770


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.

Reviews citing this publication (5)

  1. Computational virology: From the inside out. Reddy T, Sansom MS. Biochim. Biophys. Acta 1858 1610-1618 (2016)
  2. Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes. Goh BC, Hadden JA, Bernardi RC, Singharoy A, McGreevy R, Rudack T, Cassidy CK, Schulten K. Annu Rev Biophys 45 253-278 (2016)
  3. Enhanced sampling techniques in molecular dynamics simulations of biological systems. Bernardi RC, Melo MC, Schulten K. Biochim. Biophys. Acta 1850 872-877 (2015)
  4. Molecular dynamics simulations of large macromolecular complexes. Perilla JR, Goh BC, Cassidy CK, Liu B, Bernardi RC, Rudack T, Yu H, Wu Z, Schulten K. Curr. Opin. Struct. Biol. 31 64-74 (2015)
  5. Structural basis of glycan interaction in gastroenteric viral pathogens. Venkataram Prasad BV, Shanker S, Hu L, Choi JM, Crawford SE, Ramani S, Czako R, Atmar RL, Estes MK. Curr Opin Virol 7 119-127 (2014)

Articles citing this publication (20)

  1. Emergence of a new lagovirus related to Rabbit Haemorrhagic Disease Virus. Le Gall-Reculé G, Lavazza A, Marchandeau S, Bertagnoli S, Zwingelstein F, Cavadini P, Martinelli N, Lombardi G, Guérin JL, Lemaitre E, Decors A, Boucher S, Le Normand B, Capucci L. Vet. Res. 44 81 (2013)
  2. GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting. Stone JE, McGreevy R, Isralewitz B, Schulten K. Faraday Discuss. 169 265-283 (2014)
  3. Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion. Reddy T, Shorthouse D, Parton DL, Jefferys E, Fowler PW, Chavent M, Baaden M, Sansom MS. Structure 23 584-597 (2015)
  4. Structural analysis of determinants of histo-blood group antigen binding specificity in genogroup I noroviruses. Shanker S, Czako R, Sankaran B, Atmar RL, Estes MK, Prasad BV. J. Virol. 88 6168-6180 (2014)
  5. Increased virulence of rabbit haemorrhagic disease virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus). Elsworth P, Cooke BD, Kovaliski J, Sinclair R, Holmes EC, Strive T. Virology 464-465 415-423 (2014)
  6. Crystal structure of a nematode-infecting virus. Guo YR, Hryc CF, Jakana J, Jiang H, Wang D, Chiu W, Zhong W, Tao YJ. Proc. Natl. Acad. Sci. U.S.A. 111 12781-12786 (2014)
  7. Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in Australia and New Zealand. Eden JS, Kovaliski J, Duckworth JA, Swain G, Mahar JE, Strive T, Holmes EC. J. Virol. 89 9548-9558 (2015)
  8. Structural analysis of a rabbit hemorrhagic disease virus binding to histo-blood group antigens. Leuthold MM, Dalton KP, Hansman GS. J. Virol. 89 2378-2387 (2015)
  9. Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies. Shakeel S, Westerhuis BM, Ora A, Koen G, Bakker AQ, Claassen Y, Wagner K, Beaumont T, Wolthers KC, Butcher SJ. J. Virol. 89 9571-9580 (2015)
  10. Rabbit haemorrhagic disease: virus persistence and adaptation in Australia. Schwensow NI, Cooke B, Kovaliski J, Sinclair R, Peacock D, Fickel J, Sommer S. Evol Appl 7 1056-1067 (2014)
  11. Molecular evolution and antigenic variation of European brown hare syndrome virus (EBHSV). Lopes AM, Capucci L, Gavier-Widén D, Le Gall-Reculé G, Brocchi E, Barbieri I, Quéméner A, Le Pendu J, Geoghegan JL, Holmes EC, Esteves PJ, Abrantes J. Virology 468-470 104-112 (2014)
  12. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles. Bárcena J, Guerra B, Angulo I, González J, Valcárcel F, Mata CP, Castón JR, Blanco E, Alejo A. Vet. Res. 46 106 (2015)
  13. Resolving the Origin of Rabbit Hemorrhagic Disease Virus: Insights from an Investigation of the Viral Stocks Released in Australia. Eden JS, Read AJ, Duckworth JA, Strive T, Holmes EC. J. Virol. 89 12217-12220 (2015)
  14. Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives. Mahar JE, Nicholson L, Eden JS, Duchêne S, Kerr PJ, Duckworth J, Ward VK, Holmes EC, Strive T. J. Virol. 90 9317-9329 (2016)
  15. The Role of the Membrane in the Structure and Biophysical Robustness of the Dengue Virion Envelope. Reddy T, Sansom MS. Structure 24 375-382 (2016)
  16. Antigenic and Cryo-Electron Microscopy Structure Analysis of a Chimeric Sapovirus Capsid. Miyazaki N, Taylor DW, Hansman GS, Murata K. J. Virol. 90 2664-2675 (2016)
  17. CryoEM Structure Refinement by Integrating NMR Chemical Shifts with Molecular Dynamics Simulations. Perilla JR, Zhao G, Lu M, Ning J, Hou G, Byeon IL, Gronenborn AM, Polenova T, Zhang P. J Phys Chem B 121 3853-3863 (2017)
  18. Emerging rabbit haemorrhagic disease virus 2 (RHDV2) at the gates of the African continent. Martin-Alonso A, Martin-Carrillo N, Garcia-Livia K, Valladares B, Foronda P. Infect. Genet. Evol. 44 46-50 (2016)
  19. Immunogenicity of different recombinant rabbit hemorrhagic disease virus-like particles carrying CD8+ T cell epitope from chicken ovalbumin (OVA). Chen M, Song Y, Fan Z, Jiang P, Hu B, Xue J, Wei H, Wang F. Virus Res. 183 15-22 (2014)
  20. Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses. Chuang TH, Lai CY, Tseng PH, Yuan CJ, Hsu LC. PLoS ONE 9 e108808 (2014)