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Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B viruses

Oncogene volume 19, pages 4427–4431 (2000)Cite this article

Abstract

A fully effective treatment of chronic human hepatitis B virus (HBV) infection is still missing and HBV remains the first etiological agent of liver cancer. Although the viral regulatory X protein is essential for infection, its mode of action remains obscure, due the lack of an in vitro infection system. In the accompanying study, we showed the functional importance of interaction between X and the host protein UVDDB-p127, in the transactivation and apoptotic properties of the viral protein. Here, we addressed the biological role of X-UVDDB interaction in the infectious process using a genetic approach in the woodchuck virus closely related to HBV. We show that (i) mutations in X, which markedly affect UVDDB-binding, also abolished productive infection in woodchucks, (ii) in the few cases where mutant viruses led to infection, compensatory mutations had occurred in the X gene of the viral progeny, which restored correct UVDDB-binding. We conclude that efficient viral replication in vivo requires proper X-UVDDB interaction. The interaction may thus provide a novel therapeutic target for the treatment of hepatitis B.

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Acknowledgements

D Sitterlin was supported by fellowships from the ‘Ministère de l'Education Nationale et de la Recherche’ and the ‘Fondation pour la Recherche Médicale’. We thank S Whiteside, M Rosbash, F Lehembre, M Flajolet and Y Wei for helpful suggestions and critical reading of the manuscript. We thank C-A Renard for support.

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  1. Delphine Sitterlin

    Present address: EMBL, Meyerhofstr., Heidelberg, D-69117, Germany

Authors and Affiliations

  1. Institut Pasteur, Unité de recombinaison et expression génétique (INSERM U163), 28 rue du Dr Roux 75724, Paris, Cedex 15, France

    Delphine Sitterlin, Françoise Bergametti, Pierre Tiollais & Catherine Transy

  2. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, C2-005 Veterinary Medical Center, Ithaca, New York, 14853-6401, NY, USA

    Bud C Tennant

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  1. Delphine Sitterlin
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Sitterlin, D., Bergametti, F., Tiollais, P. et al. Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B viruses. Oncogene 19, 4427–4431 (2000). https://doi.org/10.1038/sj.onc.1203770

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