ERVWE1

ERVWE1, also known as Syncytin-1, is a human gene derived from an envelope gene of the endogenous retrovirus HERV-W. It encodes a fusogenic membrane protein that has been repurposed for normal human placental development. The intact open reading frame of ERVWE1 is specific to humans and some primates, reflecting its evolutionary origin from an ancient retroviral insertion.

Functionally, Syncytin-1 is expressed predominantly in placental trophoblasts and mediates cell fusion to form the multinucleated syncytiotrophoblast layer, a critical component of the placental barrier that facilitates nutrient exchange between mother and fetus. The protein is believed to bind the receptor ASCT2 (SLC1A5) to trigger membrane fusion, and it may also participate in immunomodulatory processes within the placenta.

Evolution and structure: ERVWE1 is part of the HERV-W family and represents an example of a repurposed viral gene contributing to normal mammalian physiology. The Syncytin-1 protein belongs to the class I viral envelope family, consisting of surface and transmembrane subunits, and its expression is generally restricted to the placenta in adult tissues.

Regulation and expression: ERVWE1 expression is driven by promoter elements in the long terminal repeat and is tightly regulated to restrict activity largely to placental tissue. Epigenetic mechanisms contribute to tissue-specific expression, limiting ectopic fusion events.

Clinical relevance: Abnormal ERVWE1/Syncytin-1 expression has been investigated in placental pathologies such as preeclampsia and intrauterine growth restriction, and research continues into its broader implications for reproductive biology and immune regulation. Evidence regarding other disease associations remains preliminary and requires further study.