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

Abstract

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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Acknowledgements

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, X. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis . Nature 403, 785–789 (2000). https://doi.org/10.1038/35001608

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