This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, T. C. Articles by Miyamura, T. Search for Related Content PubMed PubMed Citation Articles by Li, T. C. Articles by Miyamura, T.

 Previous Article  |  Next Article 

J. Virol., 10 1997, 7207-7213, Vol 71, No. 10
Copyright © 1997, American Society for Microbiology

Expression and self-assembly of empty virus-like particles of hepatitis E virus

TC Li, Y Yamakawa, K Suzuki, M Tatsumi, MA Razak, T Uchida, N Takeda and T Miyamura
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.

Hepatitis E virus (HEV) is a pathogenic agent that causes fecally- orally transmitted acute hepatitis. The genome, a single-stranded positive-sense RNA, encodes three forward open reading frames (ORFs), in which an approximately 2-kb structural protein is located in the 3' end. To produce HEV-like particles the structural protein, with its N terminus truncated (amino acid residues 112 to 660 of ORF2), was expressed in insect Tn5 cells by a recombinant baculovirus. In addition to the primary translation product with a molecular mass of 58 kDa, a large amount of a further-processed molecule with a molecular mass of 50 kDa was generated and efficiently released into the culture medium. Electron microscopic observation of the culture medium revealed that the 50-kDa protein self-assembled to form empty virus-like particles (VLPs). The buoyant density of the VLPs in CsCl was 1.285 g/cm3 and their diameter was 23.7 nm, a little smaller than the 27 nm of native HEV particles secreted into the bile or stools of experimentally infected monkeys. The yield of the VLPs was 1 mg per 10(7) cells as a purified form. The particles possess antigenicity similar to that of authentic HEV particles and, consequently, they appear to be a good antigen for the sensitive detection of HEV-specific immunoglobulin G (IgG) and IgM antibodies. Furthermore, the VLP may be the most promising candidate yet for an HEV vaccine, owing to its potent immunogenicity.

This article has been cited by other articles:

• Graff, J., Zhou, Y.-H., Torian, U., Nguyen, H., St. Claire, M., Yu, C., Purcell, R. H., Emerson, S. U. (2008). 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 [Abstract] [Full Text]  
• Li, T.-C., Scotti, P. D., Miyamura, T., Takeda, N. (2007). Latent Infection of a New Alphanodavirus in an Insect Cell Line. J. Virol. 81: 10890-10896 [Abstract] [Full Text]  
• Ochiai, S., Sekiguchi, S., Hayashi, A., Shimadzu, M., Ishiko, H., Matsushima-Nishiwaki, R., Kozawa, O., Yasuda, M., Deguchi, T. (2007). Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2 for oral cephalosporins in Neisseria gonorrhoeae. J Antimicrob Chemother 60: 54-60 [Abstract] [Full Text]  
• Tanaka, T., Takahashi, M., Kusano, E., Okamoto, H. (2007). Development and evaluation of an efficient cell-culture system for Hepatitis E virus. J. Gen. Virol. 88: 903-911 [Abstract] [Full Text]  
• NAKAI, I., KATO, K., MIYAZAKI, A., YOSHII, M., LI, T.-C., TAKEDA, N., TSUNEMITSU, H., IKEDA, H. (2006). DIFFERENT FECAL SHEDDING PATTERNS OF TWO COMMON STRAINS OF HEPATITIS E VIRUS AT THREE JAPANESE SWINE FARMS. Am J Trop Med Hyg 75: 1171-1177 [Abstract] [Full Text]  
• Graff, J., Torian, U., Nguyen, H., Emerson, S. U. (2006). A Bicistronic Subgenomic mRNA Encodes both the ORF2 and ORF3 Proteins of Hepatitis E Virus.. J. Virol. 80: 5919-5926 [Abstract] [Full Text]  
• LI, T.-C., SAITO, M., OGURA, G., ISHIBASHI, O., MIYAMURA, T., TAKEDA, N. (2006). SEROLOGIC EVIDENCE FOR HEPATITIS E VIRUS INFECTION IN MONGOOSE.. Am J Trop Med Hyg 74: 932-936 [Abstract] [Full Text]  
• Li, T.-C., Takeda, N., Miyamura, T., Matsuura, Y., Wang, J. C. Y., Engvall, H., Hammar, L., Xing, L., Cheng, R. H. (2005). Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus. J. Virol. 79: 12999-13006 [Abstract] [Full Text]  
• Buonaguro, L., Visciano, M. L., Tornesello, M. L., Tagliamonte, M., Biryahwaho, B., Buonaguro, F. M. (2005). Induction of Systemic and Mucosal Cross-Clade Neutralizing Antibodies in BALB/c Mice Immunized with Human Immunodeficiency Virus Type 1 Clade A Virus-Like Particles Administered by Different Routes of Inoculation. J. Virol. 79: 7059-7067 [Abstract] [Full Text]  
• Li, S.-W., Zhang, J., He, Z.-Q., Gu, Y., Liu, R.-S., Lin, J., Chen, Y.-X., Ng, M.-H., Xia, N.-S. (2005). Mutational Analysis of Essential Interactions Involved in the Assembly of Hepatitis E Virus Capsid. J. Biol. Chem. 280: 3400-3406 [Abstract] [Full Text]  
• Kar-Roy, A., Korkaya, H., Oberoi, R., Lal, S. K., Jameel, S. (2004). The Hepatitis E Virus Open Reading Frame 3 Protein Activates ERK through Binding and Inhibition of the MAPK Phosphatase. J. Biol. Chem. 279: 28345-28357 [Abstract] [Full Text]  
• Fukushi, S., Kojima, S., Takai, R., Hoshino, F. B., Oka, T., Takeda, N., Katayama, K., Kageyama, T. (2004). Poly(A)- and Primer-Independent RNA Polymerase of Norovirus. J. Virol. 78: 3889-3896 [Abstract] [Full Text]  
• Mizuo, H., Suzuki, K., Takikawa, Y., Sugai, Y., Tokita, H., Akahane, Y., Itoh, K., Gotanda, Y., Takahashi, M., Nishizawa, T., Okamoto, H. (2002). Polyphyletic Strains of Hepatitis E Virus Are Responsible for Sporadic Cases of Acute Hepatitis in Japan. J. Clin. Microbiol. 40: 3209-3218 [Abstract] [Full Text]  
• Haqshenas, G., Huang, F. F., Fenaux, M., Guenette, D. K., Pierson, F. W., Larsen, C. T., Shivaprasad, H. L., Toth, T. E., Meng, X. J. (2002). The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus. J. Gen. Virol. 83: 2201-2209 [Abstract] [Full Text]  
• Takahashi, M., Nishizawa, T., Yoshikawa, A., Sato, S., Isoda, N., Ido, K., Sugano, K., Okamoto, H. (2002). Identification of two distinct genotypes of hepatitis E virus in a Japanese patient with acute hepatitis who had not travelled abroad. J. Gen. Virol. 83: 1931-1940 [Abstract] [Full Text]  
• Tyagi, S., Korkaya, H., Zafrullah, M., Jameel, S., Lal, S. K. (2002). The Phosphorylated Form of the ORF3 Protein of Hepatitis E Virus Interacts with Its Non-glycosylated Form of the Major Capsid Protein, ORF2. J. Biol. Chem. 277: 22759-22767 [Abstract] [Full Text]  
• Baric, R. S., Yount, B., Lindesmith, L., Harrington, P. R., Greene, S. R., Tseng, F.-C., Davis, N., Johnston, R. E., Klapper, D. G., Moe, C. L. (2002). Expression and Self-Assembly of Norwalk Virus Capsid Protein from Venezuelan Equine Encephalitis Virus Replicons. J. Virol. 76: 3023-3030 [Abstract] [Full Text]  
• Haqshenas, G., Shivaprasad, H. L., Woolcock, P. R., Read, D. H., Meng, X. J. (2001). Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. J. Gen. Virol. 82: 2449-2462 [Abstract] [Full Text]  
• Magden, J., Takeda, N., Li, T., Auvinen, P., Ahola, T., Miyamura, T., Merits, A., Kaariainen, L. (2001). Virus-Specific mRNA Capping Enzyme Encoded by Hepatitis E Virus. J. Virol. 75: 6249-6255 [Abstract] [Full Text]  
• Nakai, K., Win, K. M., Oo, S. S., Arakawa, Y., Abe, K. (2001). Molecular Characteristic-Based Epidemiology of Hepatitis B, C, and E Viruses and GB Virus C/Hepatitis G Virus in Myanmar. J. Clin. Microbiol. 39: 1536-1539 [Abstract] [Full Text]  
• Tyagi, S., Jameel, S., Lal, S. K. (2001). Self-Association and Mapping of the Interaction Domain of Hepatitis E Virus ORF3 Protein. J. Virol. 75: 2493-2498 [Abstract] [Full Text]  
• Riddell, M. A., Li, F., Anderson, D. A. (2000). Identification of Immunodominant and Conformational Epitopes in the Capsid Protein of Hepatitis E Virus by Using Monoclonal Antibodies. J. Virol. 74: 8011-8017 [Abstract] [Full Text]  
• Konomi, N., Miyoshi, C., La Fuente Zerain, C., Li, T.-C., Arakawa, Y., Abe, K. (1999). Epidemiology of Hepatitis B, C, E, and G Virus Infections and Molecular Analysis of Hepatitis G Virus Isolates in Bolivia. J. Clin. Microbiol. 37: 3291-3295 [Abstract] [Full Text]  
• Torresi, J, Li, F, Locarnini, S., Anderson, D. (1999). Only the non-glycosylated fraction of hepatitis E virus capsid (open reading frame 2) protein is stable in mammalian cells. J. Gen. Virol. 80: 1185-1188 [Abstract]  
• Geissler, K., Schneider, K., Fleuchaus, A., Parrish, C. R., Sutter, G., Truyen, U. (1999). Feline Calicivirus Capsid Protein Expression and Capsid Assembly in Cultured Feline Cells. J. Virol. 73: 834-838 [Abstract] [Full Text]  
• Stephen, A. G., Raval-Fernandes, S., Huynh, T., Torres, M., Kickhoefer, V. A., Rome, L. H. (2001). Assembly of Vault-like Particles in Insect Cells Expressing Only the Major Vault Protein. J. Biol. Chem. 276: 23217-23220 [Abstract] [Full Text]  
• Lim, K. P., Liu, D. X. (2001). The Missing Link in Coronavirus Assembly. RETENTION OF THE AVIAN CORONAVIRUS INFECTIOUS BRONCHITIS VIRUS ENVELOPE PROTEIN IN THE PRE-GOLGI COMPARTMENTS AND PHYSICAL INTERACTION BETWEEN THE ENVELOPE AND MEMBRANE PROTEINS. J. Biol. Chem. 276: 17515-17523 [Abstract] [Full Text]