Table 1.

Summary of key references

Topic	Title of publication	Journal, author, time	Study subjects/model	Major conclusion	Reference
Syncytin-1 structure	The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors	J Virol; Lavillette et al.; 2002	CHO and HEK293T cells	HERV-W Env is capable of mediating syncytium formation by interacting with the human sodium-dependent neutral amino acid transporter type 2 (ASCT2)	[24]
	Synthesis, assembly, and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope	J Virol; Cheynet et al.; 2005	BeWo and TELCeB6 cells	The cellular syncytin protein is generated as a glycosylated gp73 precursor, and cleaved into the gp50 SU and the gp24 TM subunits at cleavage site RNKR	[22]
	C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity	Biol Chem; Drewlo et al.; 2006	CHO and HEK293T cells	The C-terminally truncated sequences adjoining to the transmembrane region of syncytin-1 were essential for cell fusion	[23]
Syncytin-1 and vascularization	Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene	PNAS; Dupressoir et al.; 2007	Mouse syncytin-A knockout	Placentas of syncytin-A null mice grew fewer and narrower blood vessels that contained fewer embryonic erythrocytes	[81]
	Syncytin-1 in the human placenta	Placenta; Holder et al.; 2012	Human placenta; BeWo cells	Endothelium of PE placental vessels had higher levels of syncytin-1 SU domain	[80]
	Inducible knockout of Syncytin-A gene leads to an extensive placental vasculature deficiency, implications for preeclampsia	Clin Chim Acta; Qiao et al.; 2017	Mouse Syncytin-A knockout	Placentas of syncytin-A knockout mice had decreased size and thickness, and reduced number and irregular distribution of fetal microvessels in labyrinth layer	[82]
Syncytin-1 and hypoxia	Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in preeclampsia	Biochim Biophys Acta; Kudo et al.; 2003	BeWo cells	Low oxygen atmosphere led to decreased expression of syncytin-1 and ASCT2, and inhibition of BeWo cell syncytialization	[83]
	Mechanism of hypoxia-induced GCM1 degradation: implications for the pathogenesis of preeclampsia	J Biol Chem; Chiang et al.; 2009	BeWo cells	Hypoxia downregulated syncytin-1, attenuated the syncytin-1-mediated immunosuppression, and enhanced inflammation	[84]
	A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytiolization: implication of trophoblast malfunction in preeclampsia	Biol Reprod; Wang et al.; 2019	Human placenta; BeWo cells	Hypoxia led to upregulation of HIF-1α and inhibition of syncytin-2 by decreasing CPEB expression, which was reversed by inhibition of miR-210	[85]
Sycytin-1 and immune cell responses	Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins	PNAS; Mangeney et al.; 2007	Tumor zenografts in mouse	Malignant cells expressing syncytin-2 grew larger tumors that persisted longer time, suggesting immunosuppression	[90]
	The endogenous retroviral envelope protein syncytin-1 inhibits lps/pha-stimulated cytokine responses in human blood and is sorted into placental exosomes	Placenta; Tolosa et al.; 2012	Placenta; Primary trophoblast; PBMC	Syncytin-1 was detected in placental exosomes; Syncytin-1 peptide inhibited production of Th1 cytokines TNF-α and IFN-γ by human blood cells	[88]
	Human endogenous retrovirus envelope proteins target dendritic cells to suppress T-cell activation	Eur J Immunol; Hummel et al.; 2015	CHO/BeWo cells co-culture with DC and T cells	BeWo cells overexpressing syncytin-1 suppressed T-cell proliferation and LPS-induced TNF-α and IL-12 release	[91]
Syncytin-1 and infection	Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription	Retrovirology; Assinger et al.; 2013	Cancer cell lines; Endothelial cells; Monocytes	Syncytin-1 transcription was activated by infection of CMV in human glioma GliNS1 cells	[104]
Syncytin-1 and multiple sclerosis	The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflammation and its receptor expression in multiple sclerosis: a role for endoplasmic reticulum chaperones in astrocytes	J Immunol; Antony et al.; 2007	Human brain tissue; Astrocytes; Syncytin-A transgenic mice	Astrocyte cells from MS lesion had increased syncytin-1 and decreased ASCT-1 expression; Mice overexpressing syncytin-1 displayed neuroinflammation	[114]
	Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines	Virology; Mameli et al.; 2007	Human U-87MG astrocytic cells	IL-1, IL-6, TNF-α and IFN-γ activated syncytin-1 expression by augmenting NF-κB pathway	[116]