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Journal of Virology, May 2005, p. 5585-5593, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5585-5593.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Synthesis, Assembly, and Processing of the Env ERVWE1/Syncytin Human Endogenous Retroviral Envelope

V. Cheynet,1,{dagger} A. Ruggieri,2,{dagger},{ddagger} G. Oriol,1 J.-L. Blond,1,§ B. Boson,2 L. Vachot,3 B. Verrier,3 F.-L. Cosset,2,¶* and F. Mallet1,¶*

UMR 2714 CNRS-bioMérieux,1 FRE 2736 Tour CERVI, IFR128 BioSciences Lyon-Gerland,3 Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, Ecole Normale Supérieure de Lyon, Lyon, France2

Received 5 July 2004/ Accepted 16 December 2004

Syncytin is a fusogenic protein involved in the formation of the placental syncytiotrophoblast layer. This protein is encoded by the envelope gene of the ERVWE1 proviral locus belonging to the human endogenous retrovirus W (HERV-W) family. The HERV-W infectious ancestor entered the primate lineage 25 to 40 million years ago. Although the syncytin fusion property has been clearly demonstrated, little is known about this cellular protein maturation process with respect to classical infectious retrovirus envelope proteins. Here we show that the cellular syncytin protein is synthesized as a glycosylated gPr73 precursor cleaved into two mature proteins, a gp50 surface subunit (SU) and a gp24 transmembrane subunit (TM). These SU and TM subunits are found associated as homotrimers. The intracytoplasmic tail is critical to the fusogenic phenotype, although its cleavage requirements seem to have diverged from those of classical retroviral maturation.

* Corresponding author. Mailing address for F.-L. Cosset: Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, Ecole Normale Supérieure de Lyon, 69364 Lyon, France. Phone: 33 472 728 732. Fax: 33 472 728 724. E-mail: flcosset{at}ens-lyon.fr.

* Corresponding author. Mailing address for F. Mallet: UMR 2714 CNRS-bioMérieux, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon, France. Phone: 33 472 728 358. Fax: 33 472 728 533. E-mail: francois.mallet{at}ens-lyon.fr.

{dagger} V.C. and A.R. contributed equally to this work.

{ddagger} Present address: Human Genetics, University of Saar, 66421 Homburg, Germany.

§ Present address: Unité Mixte BioMérieux-Hospices Civils de Lyon, 69003 Lyon, France.

F.M. and F.-L.C. contributed equally to this work as senior authors.

Journal of Virology, May 2005, p. 5585-5593, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5585-5593.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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