Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure
Edited by Michael G. Rossmann, Purdue University, West Lafayette, IN, and approved June 8, 2009
Abstract
Hepatitis E virus (HEV) is a causative agent of acute hepatitis. The crystal structure of HEV-like particles (HEV-LP) consisting of capsid protein was determined at 3.5-Å resolution. The capsid protein exhibited a quite different folding at the protruding and middle domains from the members of the families of Caliciviridae and Tombusviridae, while the shell domain shared the common folding. Tyr-288 at the 5-fold axis plays key roles in the assembly of HEV-LP, and aromatic amino acid residues are well conserved among the structurally related viruses. Mutational analyses indicated that the protruding domain is involved in the binding to the cells susceptive to HEV infection and has some neutralization epitopes. These structural and biological findings are important for understanding the molecular mechanisms of assembly and entry of HEV and also provide clues in the development of preventive and prophylactic measures for hepatitis E.
Data Availability
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2ZTN).
Acknowledgments.
We thank H. Murase for her secretarial work and the staff of SPring-8 BL44XU beamline and synchrotron beamline NW-17A of the Photon Factory, High Energy Accelerator Research Organization for their assistance with the data collection. This work was supported in part by grants-in-aid from the Research and Development Program for New Bio-industry Initiatives of Bio-oriented Technology Research Advancement Institution (BRAIN) and the Foundation for Research Collaboration Center on Emerging and Re-emerging Infections.
Supporting Information
Supporting Information (PDF)
Supporting Information
- Download
- 2.46 MB
References
1
SK Panda, D Thakral, S Rehman, Hepatitis E virus. Rev Med Virol 17, 151–180 (2007).
2
RH Purcell, SU Emerson, Hepatitis E: An emerging awareness of an old disease. J Hepatol 48, 494–503 (2008).
3
U Navaneethan, M Al Mohajer, MT Shata, Hepatitis E and pregnancy: Understanding the pathogenesis. Liver Int 28, 1190–1199 (2008).
4
XJ Meng, et al., A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci USA 94, 9860–9865 (1997).
5
H Sonoda, et al., Prevalence of hepatitis E virus (HEV) Infection in wild boars and deer and genetic identification of a genotype 3 HEV from a boar in Japan. J Clin Microbiol 42, 5371–5374 (2004).
6
H Okamoto, Genetic variability and evolution of hepatitis E virus. Virus Res 127, 216–228 (2007).
7
TC Li, et al., Hepatitis E virus transmission from wild boar meat. Emerg Infect Dis 11, 1958–1960 (2005).
8
Y Yazaki, et al., Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J Gen Virol 84, 2351–2357 (2003).
9
AW Tam, et al., Hepatitis E virus (HEV): Molecular cloning and sequencing of the full-length viral genome. Virology 185, 120–131 (1991).
10
K Matsubayashi, et al., Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 44, 934–940 (2004).
11
FF Huang, et al., Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV. J Gen Virol 85, 1609–1618 (2004).
12
SU Emerson, et al., Putative neutralization epitopes and broad cross-genotype neutralization of Hepatitis E virus confirmed by a quantitative cell-culture assay. J Gen Virol 87, 697–704 (2006).
13
S He, et al., Putative receptor-binding sites of hepatitis E virus. J Gen Virol 89, 245–249 (2008).
14
J Meng, et al., Identification and characterization of the neutralization epitope(s) of the hepatitis E virus. Virology 288, 203–211 (2001).
15
M Takahashi, et al., Production of monoclonal antibodies against hepatitis E virus capsid protein and evaluation of their neutralizing activity in a cell culture system. Arch Virol 153, 657–666 (2008).
16
DJ Schofield, J Glamann, SU Emerson, RH Purcell, Identification by phage display and characterization of two neutralizing chimpanzee monoclonal antibodies to the hepatitis E virus capsid protein. J Virol 74, 5548–5555 (2000).
17
DJ Schofield, RH Purcell, HT Nguyen, SU Emerson, Monoclonal antibodies that neutralize HEV recognize an antigenic site at the carboxyterminus of an ORF2 protein vaccine. Vaccine 22, 257–267 (2003).
18
J Graff, et al., Mutations within potential glycosylation sites in the capsid protein of hepatitis E virus prevent the formation of infectious virus particles. J Virol 82, 1185–1194 (2008).
19
M Zafrullah, MH Ozdener, R Kumar, SK Panda, S Jameel, Mutational analysis of glycosylation, membrane translocation, and cell surface expression of the hepatitis E virus ORF2 protein. J Virol 73, 4074–4082 (1999).
20
R Huang, et al., Cell culture of sporadic hepatitis E virus in China. Clin Diagn Lab Immunol 6, 729–733 (1999).
21
A Kazachkov Yu, et al., Hepatitis E virus in cultivated cells. Arch Virol 127, 399–402 (1992).
22
J Meng, P Dubreuil, J Pillot, A new PCR-based seroneutralization assay in cell culture for diagnosis of hepatitis E. J Clin Microbiol 35, 1373–1377 (1997).
23
AW Tam, et al., In vitro infection and replication of hepatitis E virus in primary cynomolgus macaque hepatocytes. Virology 238, 94–102 (1997).
24
T Tanaka, M Takahashi, E Kusano, H Okamoto, Development and evaluation of an efficient cell-culture system for Hepatitis E virus. J Gen Virol 88, 903–911 (2007).
25
D Bradley, et al., Aetiological agent of enterically transmitted non-A, non-B hepatitis. J Gen Virol 69, 731–738 (1988).
26
TC Li, et al., Expression and self-assembly of empty virus-like particles of hepatitis E virus. J Virol 71, 7207–7213 (1997).
27
TC Li, et al., Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus. J Virol 79, 12999–13006 (2005).
28
L Xing, et al., Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes. Virology 265, 35–45 (1999).
29
BV Prasad, et al., X-ray crystallographic structure of the Norwalk virus capsid. Science 286, 287–290 (1999).
30
R Chen, JD Neill, MK Estes, BV Prasad, X-ray structure of a native calicivirus: Structural insights into antigenic diversity and host specificity. Proc Natl Acad Sci USA 103, 8048–8053 (2006).
31
E Morgunova, et al., The atomic structure of Carnation Mottle Virus capsid protein. FEBS Lett 338, 267–271 (1994).
32
JM Hogle, M Chow, DJ Filman, Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229, 1358–1365 (1985).
33
J Tsao, et al., The three-dimensional structure of canine parvovirus and its functional implications. Science 251, 1456–1464 (1991).
34
D Bhella, D Gatherer, Y Chaudhry, R Pink, IG Goodfellow, Structural insights into calicivirus attachment and uncoating. J Virol 82, 8051–8058 (2008).
35
W Bu, et al., Structural basis for the receptor binding specificity of Norwalk virus. J Virol 82, 5340–5347 (2008).
36
JM Choi, AM Hutson, MK Estes, BV Prasad, Atomic resolution structural characterization of recognition of histo-blood group antigens by Norwalk virus. Proc Natl Acad Sci USA 105, 9175–9180 (2008).
37
TC Li, et al., Protection of cynomolgus monkeys against HEV infection by oral administration of recombinant hepatitis E virus-like particles. Vaccine 22, 370–377 (2004).
38
C Hsu, et al., Characterization of polymorphism displayed by the coat protein mutants of tomato bushy stunt virus. Virology 349, 222–229 (2006).
39
K Kakani, R Reade, U Katpally, T Smith, D Rochon, Induction of particle polymorphism by cucumber necrosis virus coat protein mutants in vivo. J Virol 82, 1547–1557 (2008).
40
LJ White, ME Hardy, MK Estes, Biochemical characterization of a smaller form of recombinant Norwalk virus capsids assembled in insect cells. J Virol 71, 8066–8072 (1997).
41
DM Belnap, et al., Molecular tectonic model of virus structural transitions: The putative cell entry states of poliovirus. J Virol 74, 1342–1354 (2000).
42
D Bubeck, DJ Filman, JM Hogle, Cryo-electron microscopy reconstruction of a poliovirus-receptor-membrane complex. Nat Struct Mol Biol 12, 615–618 (2005).
43
H Jayaram, MK Estes, BV Prasad, Emerging themes in rotavirus cell entry, genome organization, transcription and replication. Virus Res 101, 67–81 (2004).
Information & Authors
Information
Published in
Cover image: Pictured is a microbial mat growing near White Creek in Yellowstone National Park. These microbial communities produce lipids with unusually large variations in their deuterium content. Zhang et al. show that such variations likely relate to the different metabolic pathways employed by the microbes and suggest that deuterium variations in ancient lipids could be used to identify pathways of energy metabolism active in the past. See the Feature Article by Xinning Zhang et al. on pages 12580–12586. Image by Alex Sessions.
Classifications
Copyright
© 2009.
Data Availability
Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2ZTN).
Submission history
Received: April 3, 2009
Published online: August 4, 2009
Published in issue: August 4, 2009
Keywords
Acknowledgments
We thank H. Murase for her secretarial work and the staff of SPring-8 BL44XU beamline and synchrotron beamline NW-17A of the Photon Factory, High Energy Accelerator Research Organization for their assistance with the data collection. This work was supported in part by grants-in-aid from the Research and Development Program for New Bio-industry Initiatives of Bio-oriented Technology Research Advancement Institution (BRAIN) and the Foundation for Research Collaboration Center on Emerging and Re-emerging Infections.
Notes
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0903699106/DCSupplemental.
Authors
Competing Interests
The authors declare no conflict of interest.
Metrics & Citations
Metrics
Citation statements
Altmetrics
Citations
Cite this article
106 (31) 12986-12991,
Export the article citation data by selecting a format from the list below and clicking Export.
Cited by
Loading...
View Options
View options
PDF format
Download this article as a PDF file
DOWNLOAD PDFLogin options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginRecommend to a librarian
Recommend PNAS to a LibrarianPurchase options
Purchase this article to access the full text.