1.G.9 The Syncytin (Syncytin) Family
Syncytin-1 of the endogenous defective retrovirus HERV-W, is a 'captive' retroviral envelope protein involved in placental morphogenesis (Mi et al., 2000). The viral protein has assumed an important function in mammalian physiology. Expression of recombinant syncytin induces formation of giant syncytia, and fusion of a human trophoblast cell line is mediated by syncytin. Thus, syncytin, a probable viral membrane fusion protein, mediates placental cytotrophoblast fusion in vivo, and thus is important for human placental morphogenesis (Mi et al., 2000). The ERVW-1 receptor is SLC1A5/ASCT-2/RDR/ATB0, a sodium-dependent neutral amino acid transporter B0 (2.A.23.3.3), and their interaction is mediated by connexin 43. Both proteins are essential for trophoblast cell fusion (Dunk et al., 2012). Fusion in the placenta is facilitated by syncytin 1 and syncytin 2. These syncytins arose from retroviral sequences that entered the primate genome 25 million and more than 40 million years ago, respectively. Syncytins and their receptors are involved in fusion events during human reproduction and during tumorigenesis. (Soygur and Sati 2016). The effects of individually silenced N-glycosylation sites and non-synonymous single-nucleotide polymorphisms on the fusogenic function of human syncytin-2 have been demonstrated (Cui et al. 2016).Syncytins have bee reviewed by Hernández and Podbilewicz 2017.
HERV-W_7q21.2 provirus ancestral Env polyprotein (ENV-W; gPr73; enverin; syncytin-1, HERV-7q envelope protein) (Blond et al., 1999; Mi et al., 2000). This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. It may induce fusion through binding of SLC1A4 and SLC1A5 (Blond et al. 2000; Lavillette et al. 2002; Sugimoto et al. 2013. Syncytin-1 interacts with the ASCT2 receptor (Štafl et al. 2021).
HERV-W_7q21.2 of Homo sapiens (Q9UQF0)
Syncytin 2 of 538 aas. Syncytins maintain cell-cell fusogenic activity based on ENV: gene-mediated viral cell entry but promote fusion of various cells during development in humans (Soygur and Sati 2016).
Syncytin 2 of Homo sapiens
Envelope glycoprotein, Env
Env of porcine endogenous retrovirus A
The human T-lymphotropic virus type 1 (HTLV-1) glycoprotein gp21 of 121 aas and containing the N-terminal 25 aa fusion peptide with a single TMS.
gp21 of the human T-lymphotropic virus type 1 (HTLV-1)
The Human T-cell leukemia virus 1, HTLV-1, of 488 aas and 2 TMSs, N- and C-terminal. The glycine-rich region of this transmembrane protein is involved in membrane fusion. It is a class I viral fusion protein (Wilson et al. 2005). The N-terminal fusion peptide initiates virus-cell membrane fusion. The fusion peptide is linked to the coiled-coil core through a conserved sequence that is rich in glycines. Wilson et al. 2005 investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of gp21. Alanine substitution for the hydrophobic residue Ile-334 caused a 90% reduction in cell-cell fusion activity without a detectable effect on the lipid-mixing and pore forming phases of fusion. Retroviral glycoprotein fusion thus appears to require flexibility within the glycine-rich segment and hydrophobic contacts mediated by this segment (Wilson et al. 2005).
HTLV-1 of T-cell leukemia virus 1
Envelope glycoprotein of 259 aas, Env
Env of Human T-cell leukemia virus 2 (HTLV-2)
Envelope glycoprotein of 214 aas (partial) Gp30.
Gp30 of bovine leukemia viru
Envolope glycoprotein of 341 aas and 3 TMSs, one N-terminal and two C-terminal, gPr72. Three YXXL sequences of a Bovine Leukemia Virus TEnv transmembrane protein are independently required for fusion activity by controlling expression on the cell membrane (Matsuura et al. 2019). The fusion peptide mediates fusion of the viral envelop with the cell membrane (Meher and Chakraborty 2020).
Env protein of bovine leukemia virus