- Hepatitis C virus
- Chronic hepatitis
- MxA protein
- MxA gene
- Single nucleotide polymorphism
We have previously reported a single nucleotide polymorphism (SNP) at nucleotide (nt) position –88 (G or T) within an interferon-stimulated response element-like sequence in the promoter region of the MxA gene, which correlated with responsiveness of hepatitis C patients to interferon. Upstream of it, we then identified another SNP (C or A at nt –123) and investigated whether this SNP also correlates with interferon responsiveness. The two SNPs showed a high linkage to each other: all the individuals having G at –88 had C at –123, and 73% of those having T at –88 had A at –123. As was expected from this observation, the SNP at –123 also exhibited a correlation with interferon responsiveness (C/C homozygotes were more frequent among nonresponders than among responders: 65% of 107 vs. 40% of 52, p = 0.0028). These in vivo data from patients were further supported by results from in vitro experiments. The MxA promoter sequence with A at –123 and T at –88 showed about 4-fold higher activity of upregulating the downstream reporter gene than that with C at –123 and G at –88, in a luciferase reporter assay.
Copyright © 2002 S. Karger AG, Basel
- Arnheiter H, Haller O, Lindenmann J: Pathology of influenza hepatitis in susceptible and genetically resistant mice. Exp Cell Biol 1976;44:95–107.
- Pitossi F, Blank A, Schroder A, Schwarz A, Hussi P, Schwemmle M, Pavlovic J, Staeheli P: A functional GTP-binding motif is necessary for antiviral activity of Mx proteins. J Virol 1993;67:6726–6732.
- Pavlovic J, Zucher T, Haller O, Staeheli P: Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J Virol 1990;64:3370–3375.
- Zhao H, De BP, Das T, Banerjee AK: Inhibition of human parainfluenza virus-3 replication by interferon and human MxA. Virology 1996;220:330–338.
- Landis H, Simon-Jödicke A, Klöti A, Di Paolo C, Schnorr JJ, Schneider-Schaulies S, Hefti HP, Pavlovic J: Human MxA protein confers resistance to Semliki Forest virus and inhibits the amplification of a Semliki Forest virus-based replicon in the absence of viral structural proteins. J Virol 1998;72:1516–1522.
- Chieux V, Hober D, Harvey J, Lion G, Lucidarme D, Forzy G, Duhamel M, Cousin J, Ducoulombier H, Wattré P: The MxA protein levels in whole blood lysates of patients with various viral infections. J Virol Methods 1998;70:183–191.
- Chang KC, Hansen E, Foroni L, Lida J, Goldspink G: Molecular and functional analysis of the virus- and interferon-inducible human MxA promoter. Arch Virol 1991;117:1–15.
- Nakade K, Handa H, Nagata K: Promoter structure of the MxA gene that confers resistance to influenza virus. FEBS Lett 1997;418:315–318.
- Ronni T, Matikainen S, Lehtonen A, Palvimo J, Dellis J, Van Bylen F, Goetschy J-F, Horisberger M, Content J, Julkunen I: The proximal interferon-stimulated response elements are essential for interferon responsiveness: A promoter analysis of the antiviral MxA gene. J Interferon Cytokine Res 1988;18:773–781.
- Hijikata M, Ohta Y, Mishiro S: Identification of a single nucleotide polymorphism in the MxA gene promoter (G/T at nt –88) correlated with the response of hepatitis C patients to interferon. Intervirology 2000;43:124–127.
Dr. Shunji Mishiro, MD
Department of Medical Sciences
Toshiba General Hospital
6-3-22 Higashi Oh-i, Shinagawa-ku, Tokyo 140-8522 (Japan)
Tel. +81 3 3764 8981, Fax +81 3 3764 8992, E-Mail firstname.lastname@example.org
Received: Received: July 31, 2001
Accepted after revision: September 3, 2001
Number of Print Pages : 4
Number of Figures : 2, Number of Tables : 3, Number of References : 10
Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)
Vol. 44, No. 6, Year 2001 (Cover Date: November-December 2001 (Released January 2002))
Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)
For additional information: http://www.karger.com/journals/int
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.