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Originally published In Press as doi:10.1074/jbc.C901002199 on June 12, 2000

J. Biol. Chem., Vol. 275, Issue 31, 23417-23420, August 4, 2000
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ACCELERATED PUBLICATION
Definition of an Amino-terminal Domain of the Human T-cell Leukemia Virus Type 1 Envelope Surface Unit That Extends the Fusogenic Range of an Ecotropic Murine Leukemia Virus*

Felix J. KimDagger §, Iban SeiliezDagger , Caroline Denesvre||, Dimitri Lavillette**, François-Loïc Cosset**, and Marc SitbonDagger Dagger Dagger

From the Dagger  Institut de Génétique Moléculaire de Montpellier, IFR24, CNRS-UMR5535 and Université Montpellier II, 1919 Rte de Mende, F-34293 Montpellier Cedex 05, ** LVRTG, INSERM U412, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69367 Lyon Cedex 07, and  Institut Cochin de Génétique Moléculaire, 22 Rue Méchain, 75014 Paris, France

Murine leukemia viruses (MuLV) and human T-cell leukemia viruses (HTLV) are phylogenetically highly divergent retroviruses with distinct envelope fusion properties. The MuLV envelope glycoprotein surface unit (SU) comprises a receptor-binding domain followed by a proline-rich region which modulates envelope conformational changes and fusogenicity. In contrast, the receptor-binding domain and SU organization of HTLV are undefined. Here, we describe an HTLV/MuLV envelope chimera in which the receptor-binding domain and proline-rich region of the ecotropic MuLV were replaced with the potentially corresponding domains of the HTLV-1 SU. This chimeric HTLV/MuLV envelope was processed, specifically interfered with HTLV-1 envelope-mediated fusion, and similar to MuLV envelopes, required cleavage of its cytoplasmic tail to exert significant fusogenic properties. Furthermore, the HTLV domain defined here broadened ecotropic MuLV envelope-induced fusion to human and simian cell lines.

* This work was supported by successive grants (to M. S.) from the CNRS (ATIPE virology program), the Fondation pour la Recherche Médicale (Jeune Équipe program), the Association pour la Recherche sur le Cancer (ARC 4066), the Association Française contre les Myopathies (AFM 6889), and the Agence Nationale pour la Recherche contre le SIDA (ANRS 99003).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by an award from the Philippe Foundation and an ANRS graduate student fellowship.

|| Present address: Unité INRA/ENVA de Génétique Moléculaire et Cellulaire, Génétique Virale, 94704 Maisons-Alfort Cedex, France.

Dagger Dagger Supported by the Institut National de la Santé et de la Recherche Médicale. To whom correspondence should be addressed: Institut de Génétique Moléculaire de Montpellier (IGMM), CNRS-UMR5535, 1919 Rte. de Mende, F-34293 Montpellier Cedex 5, France. Tel.: +33-467-613-640; Fax: +33-467-040-231; E-mail: sitbon@jones.igm.cnrs-mop.fr.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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