Letters to Nature

Nature 403, 785-789 (17 February 2000) | doi:10.1038/35001608; Received 29 April 1999; Accepted 20 December 1999

Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis

Sha Mi, Xinhua Lee, Xiang-ping Li, Geertruida M. Veldman, Heather Finnerty, Lisa Racie, Edward LaVallie, Xiang-Yang Tang, Philippe Edouard, Steve Howes, James C. Keith, Jr & John M. McCoy1

  1. Genetics Institute, Inc., 87 CambridgePark Drive, Cambridge, Massachusetts 02140, USA
  2. Present address: Biogen Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA

Correspondence to: John M. McCoy1 Correspondence should be directed to J.M.M. (e-mail Email:  john_mccoy@biogen.com) or S.M. (e-mail Email: smi@genetics.com). Requests for materials should be directed to S.M. The sequence of the syncytin cDNA used in this work can be found in GenBank, accession no. AF208161.

Many mammalian viruses have acquired genes from their hosts during their evolution1. The rationale for these acquisitions is usually quite clear: the captured genes are subverted to provide a selective advantage to the virus. Here we describe the opposite situation, where a viral gene has been sequestered to serve an important function in the physiology of a mammalian host. This gene, encoding a protein that we have called syncytin, is the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W2. We find that the major sites of syncytin expression are placental syncytiotrophoblasts, multinucleated cells that originate from fetal trophoblasts. We show that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibited by an anti-syncytin antiserum. Our data indicate that syncytin may mediate placental cytotrophoblast fusion in vivo, and thus may be important in human placental morphogenesis.