This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Magden, J.
Right arrow Articles by Kääriäinen, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Magden, J.
Right arrow Articles by Kääriäinen, L.

Next Article 

Journal of Virology, July 2001, p. 6249-6255, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6249-6255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Virus-Specific mRNA Capping Enzyme Encoded by Hepatitis E Virus

Julia Magden,1 Naokazu Takeda,2 Tiancheng Li,2 Petri Auvinen,1 Tero Ahola,1,dagger Tatsuo Miyamura,2 Andres Merits,1 and Leevi Kääriäinen1,*

Program in Cellular Biotechnology, Institute of Biotechnology, Viikki Biocenter, 00014 University of Helsinki, Finland,1 and Department of Virology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan2

Received 1 February 2001/Accepted 19 April 2001

Hepatitis E virus (HEV), a positive-strand RNA virus, is an important causative agent of waterborne hepatitis. Expression of cDNA (encoding amino acids 1 to 979 of HEV nonstructural open reading frame 1) in insect cells resulted in synthesis of a 110-kDa protein (P110), a fraction of which was proteolytically processed to an 80-kDa protein. P110 was tightly bound to cytoplasmic membranes, from which it could be released by detergents. Immunopurified P110 catalyzed transfer of a methyl group from S-adenosylmethionine (AdoMet) to GTP and GDP to yield m7GTP or m7GDP. GMP, GpppG, and GpppA were poor substrates for the P110 methyltransferase. There was no evidence for further methylation of m7GTP when it was used as a substrate for the methyltransferase. P110 was also a guanylyltransferase, which formed a covalent complex, P110-m7GMP, in the presence of AdoMet and GTP, because radioactivity from both [alpha -32P]GTP and [3H-methyl]AdoMet was found in the covalent guanylate complex. Since both methyltransferase and guanylyltransferase reactions are strictly virus specific, they should offer optimal targets for development of antiviral drugs. Cap analogs such as m7GTP, m7GDP, et2m7GMP, and m2et7GMP inhibited the methyltransferase reaction. HEV P110 capping enzyme has similar properties to the methyltransferase and guanylyltransferase of alphavirus nsP1, tobacco mosaic virus P126, brome mosaic virus replicase protein 1a, and bamboo mosaic virus (a potexvirus) nonstructural protein, indicating there is a common evolutionary origin of these distantly related plant and animal virus families.


* Corresponding author. Mailing address: Institute of Biotechnology, Viikki Biocenter, PO Box 56 (Viikinkaari 9), 00014 University of Helsinki, Finland. Phone: 358-9-19159400. Fax: 358-9-191 59560. E-mail: leevi.kaariainen{at}helsinki.fi.

dagger Present address: Pfizer Global Research and Development, Sandwich, Kent, United Kingdom.


Journal of Virology, July 2001, p. 6249-6255, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6249-6255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Rancurel, C., Khosravi, M., Dunker, A. K., Romero, P. R., Karlin, D. (2009). Overlapping Genes Produce Proteins with Unusual Sequence Properties and Offer Insight into De Novo Protein Creation. J. Virol. 83: 10719-10736 [Abstract] [Full Text]  
  • Cheng, C.-W., Hsiao, Y.-Y., Wu, H.-C., Chuang, C.-M., Chen, J.-S., Tsai, C.-H., Hsu, Y.-H., Wu, Y.-C., Lee, C.-C., Meng, M. (2009). Suppression of Bamboo Mosaic Virus Accumulation by a Putative Methyltransferase in Nicotiana benthamiana. J. Virol. 83: 5796-5805 [Abstract] [Full Text]  
  • Yamada, K., Takahashi, M., Hoshino, Y., Takahashi, H., Ichiyama, K., Tanaka, T., Okamoto, H. (2009). Construction of an infectious cDNA clone of hepatitis E virus strain JE03-1760F that can propagate efficiently in cultured cells. J. Gen. Virol. 90: 457-462 [Abstract] [Full Text]  
  • Van Wynsberghe, P. M., Chen, H.-R., Ahlquist, P. (2007). Nodavirus RNA Replication Protein A Induces Membrane Association of Genomic RNA. J. Virol. 81: 4633-4644 [Abstract] [Full Text]  
  • Emerson, S. U., Nguyen, H., Torian, U., Purcell, R. H. (2006). ORF3 Protein of Hepatitis E Virus Is Not Required for Replication, Virion Assembly, or Infection of Hepatoma Cells In Vitro. J. Virol. 80: 10457-10464 [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., 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]  
  • van Cuyck, H., Fan, J., Robertson, D. L., Roques, P. (2005). Evidence of Recombination between Divergent Hepatitis E Viruses. J. Virol. 79: 9306-9314 [Abstract] [Full Text]  
  • Thakral, D., Nayak, B., Rehman, S., Durgapal, H., Panda, S. K. (2005). Replication of a recombinant hepatitis E virus genome tagged with reporter genes and generation of a short-term cell line producing viral RNA and proteins. J. Gen. Virol. 86: 1189-1200 [Abstract] [Full Text]  
  • Huang, Y.-L., Hsu, Y.-H., Han, Y.-T., Meng, M. (2005). mRNA Guanylation Catalyzed by the S-Adenosylmethionine-dependent Guanylyltransferase of Bamboo Mosaic Virus. J. Biol. Chem. 280: 13153-13162 [Abstract] [Full Text]  
  • Graff, J., Nguyen, H., Kasorndorkbua, C., Halbur, P. G., St. Claire, M., Purcell, R. H., Emerson, S. U. (2005). In Vitro and In Vivo Mutational Analysis of the 3'-Terminal Regions of Hepatitis E Virus Genomes and Replicons. J. Virol. 79: 1017-1026 [Abstract] [Full Text]  
  • Emerson, S. U., Nguyen, H., Graff, J., Stephany, D. A., Brockington, A., Purcell, R. H. (2004). In Vitro Replication of Hepatitis E Virus (HEV) Genomes and of an HEV Replicon Expressing Green Fluorescent Protein. J. Virol. 78: 4838-4846 [Abstract] [Full Text]  
  • Huang, Y.-L., Han, Y.-T., Chang, Y.-T., Hsu, Y.-H., Meng, M. (2004). Critical Residues for GTP Methylation and Formation of the Covalent m7GMP-Enzyme Intermediate in the Capping Enzyme Domain of Bamboo Mosaic Virus. J. Virol. 78: 1271-1280 [Abstract] [Full Text]  
  • Salonen, A., Vasiljeva, L., Merits, A., Magden, J., Jokitalo, E., Kaariainen, L. (2003). Properly Folded Nonstructural Polyprotein Directs the Semliki Forest Virus Replication Complex to the Endosomal Compartment. J. Virol. 77: 1691-1702 [Abstract] [Full Text]  
  • Vlot, A. C., Menard, A., Bol, J. F. (2002). Role of the Alfalfa Mosaic Virus Methyltransferase-Like Domain in Negative-Strand RNA Synthesis. J. Virol. 76: 11321-11328 [Abstract] [Full Text]  
  • Emerson, S. U., Zhang, M., Meng, X.-J., Nguyen, H., St. Claire, M., Govindarajan, S., Huang, Y. K., Purcell, R. H. (2001). Recombinant hepatitis E virus genomes infectious for primates: Importance of capping and discovery of a cis-reactive element. Proc. Natl. Acad. Sci. USA 10.1073/pnas.251555098v1 [Abstract] [Full Text]  
  • Emerson, S. U., Zhang, M., Meng, X.-J., Nguyen, H., St. Claire, M., Govindarajan, S., Huang, Y. K., Purcell, R. H. (2001). Recombinant hepatitis E virus genomes infectious for primates: Importance of capping and discovery of a cis-reactive element. Proc. Natl. Acad. Sci. USA 98: 15270-15275 [Abstract] [Full Text]