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

Abstract

Many mammalian viruses have acquired genes from their hosts during their evolution. 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-W. 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.

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

“…(1)(2)(3) Thus understanding mechanisms underlying cell-cell fusion has implications for both development and tissue engineering. Various molecules are reportedly essential for cell-cell fusion of specific cell types, including dendritic cell-specific transmembrane protein (DC-STAMP) for osteoclasts and FBGCs, (3) syncytin for placenta, (4) Izumo and CD9 for sperm and eggs, (5)(6)(7)(8) respectively, and Loner for myoblasts. (9) However, signal transduction pathways governing cell-cell fusion in these cell types remain largely unclear.…”

Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer

“…Due to this fusogenic activity, this retrovirus is known to play a role in human placental morphogenesis. [16][17][18] RD and GALV are C-type mammalian retroviruses. RD envelope protein shares the common cell-surface receptor as HERV-W, 19,20 while GALV enter cells after binding with type-III sodium-dependent phosphate transporters PiT-1.…”

Silver nanoparticles exhibit size-dependent differential toxicity and induce expression of syncytin-1 in FA-AML1 and MOLT-4 leukaemia cell lines

“…In normal cells expression of syncytin-1 is mostly confined to the placenta (37) where it functions to promote both proliferation (38) and fusion of trophoblasts (39,40) in order to form syncytio-trophoblasts. It is also know to suppress apoptosis in choriocarcinoma cells (41) and low levels of syncytin-1 have been linked to placental dysfunction in pre-eclampsia (42)(43)(44).…”