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


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.

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Figure 1: Primary sequence and hydrophobicity plot of human syncytin.
Figure 2: Syncytin gene distribution and expression. a, Northern blots showing syncytin expression in human tissues.
Figure 3: In situ hybridizations and syncytin-mediated COS cell fusion.
Figure 4: Fusion of BeWo choriocarcinoma cells to GFP-labelled COS cells.

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We thank the Genetics Institute signal sequence trap team for the initial cloning of syncytin; J. Wooters for help in liposome preparations; B. Gimlich, I. Moutsatsos and the Genetics Institute Developmental Biology group for microscopy assistance; the Genetics Institute DNA synthesis group for oligonucleotides; and M. Davies, R. Pijnenborg and K. Turner for critical review of this manuscript.

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Correspondence to John M. McCoy.

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Mi, S., Lee, X., Li, Xp. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis . Nature 403, 785–789 (2000).

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