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Journal of Virology, April 2001, p. 3685-3695, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3685-3695.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activation of Membrane Fusion by Murine Leukemia Viruses Is Controlled in cis or in trans by Interactions between the Receptor-Binding Domain and a Conserved Disulfide Loop of the Carboxy Terminus of the Surface Glycoprotein

Dimitri Lavillette,1 Bertrand Boson,1 Stephen J. Russell,2 and François-Loïc Cosset1,*

Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, Ecole Normale Supérieure de Lyon and IFR 74, Lyon, France,1 and Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota2

Received 29 November 2000/Accepted 5 January 2001

Cell entry of retroviruses is initiated by the recognition of cellular receptors and the subsequent membrane fusion between viral and cellular membranes. These two steps are mediated by the surface (SU) and transmembrane (TM) subunits of the retroviral envelope glycoprotein (Env), respectively. Determinants regulating membrane fusion have been described throughout SU and TM, but the processes coupling receptor recognition to fusion are still elusive. Here we establish that a critical interaction is formed between the receptor-binding domain (RBD) and the major disulfide loop of the carboxy-terminal domain (C domain) of the murine leukemia virus SU. Receptor binding causes an alteration of this interaction and, in turn, promotes further events of Env fusion activation. We characterize mutations which, by lowering this interaction and reducing the compatibility between the RBD and C domains of Env glycoprotein chimeras, affect both Env fusogenicity and sensitivity to receptor interference. Additionally, we demonstrate that suboptimal interactions in such mutant Env proteins can be compensated in trans by soluble RBDs in a manner that depends on their compatibility with the C domain. Our results therefore indicate that RBD/C domain interactions may occur in cis, via the proper RBD of the viral Env itself, or in trans, via a distinct RBD expressed by virion-free Env glycoproteins expressed endogenously by the infected cells or provided by neighboring Env trimers.


* Corresponding author. Mailing address: LVRTG, U412, ENS de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Phone and Fax: 33 472 72 87 32. E-Mail: flcosset{at}ens-lyon.fr.


Journal of Virology, April 2001, p. 3685-3695, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3685-3695.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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