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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.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.