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

Many mammalian viruses have acquired genes from their hosts during their ev olution(1). The rationale for these acquisitions is usually quite clear: th e captured genes are subverted to provide a selective advantage to the viru s. Here we describe the opposite situation, where a viral gene has been seq uestered to serve an important function in the physiology of a mammalian ho st. This gene, encoding a protein that we have called syncytin, is the enve lope gene of a recently identified human endogenous defective retrovirus, H ERV-W-2. We find that the major sites of syncytin expression are placental syncytiotrophoblasts, multinucleated cells that originate from fetal tropho blasts. We show that expression of recombinant syncytin in a wide variety o f cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibit ed by an anti-syncytin antiserum. Our data indicate that syncytin may media te placental cytotrophoblast fusion in vivo, and thus may be important in h uman placental morphogenesis.