Functions of the fusogenic and non-fusogenic activities of Syncytin-1 in human physiological and pathological processes

Abstract

Human endogenous retroviruses (HERVs), which represent the genetic remnants of ancient viral infections, constitute approximately 8 % of the human genome. Among the proteins encoded by these viruses, Syncytin-1, encoded by the env gene of the HERV-W family, functions as a vital fusion protein in placental development, in which it plays a pivotal role in facilitating the fusion of trophoblast cells to form the syncytiotrophoblast that is essential for maintaining the structural integrity and functional viability of the placenta. Recent studies have shown that in addition to its expression in the placenta, Syncytin-1 also plays key roles in a range of different tissues and cell types, influencing biological processes such as cell proliferation, apoptosis, and immune regulation. Abnormal expression of Syncytin-1 has been closely linked to the onset, progression, and metastasis of tumors, potentially promoting tumor invasion via mechanisms involving cell fusion and modulation of the immune microenvironment. Moreover, associations have been established between Syncytin-1 and neurological disorders, including multiple sclerosis and schizophrenia, in which it modulates neuroinflammation. In this review, we systematically examine the molecular structure and functional attributes of Syncytin-1, emphasizing its roles in cell fusion, tumor progression, and immune regulation, and discuss its potential applications as a therapeutic target and diagnostic biomarker.