ERV3-1

The ERV3-1 gene encodes the ERV3-1 envelope glycoprotein, also known as HERV-R_3q12.2 Env or endogenous retrovirus group 3 member 1 envelope protein. This transmembrane protein retains ancestral retroviral fusogenic properties, potentially mediating cell-cell fusion and immune modulation. Mechanistically, it interacts with host receptors such as ASCT1/2 to facilitate membrane fusion, while its immunosuppressive domain may inhibit T-cell activation by suppressing NF-κB signaling. ERV3-1 is implicated in placental development through syncytiotrophoblast formation and participates in immune tolerance pathways, including interferon-γ (IFN-γ) and Toll-like receptor (TLR) cascades. Dysregulation correlates with autoimmune disorders like lupus and rheumatoid arthritis, as well as cancers via genomic instability induction.
Aberrant ERV3-1 expression is associated with trophoblastic diseases, testicular germ cell tumors, and melanoma progression. Its immunomodulatory properties have spurred therapeutic exploration, including anti-ERV3-1 monoclonal antibodies (e.g., 6A2D12) in Phase I trials for autoimmune conditions. Small-molecule inhibitors targeting its immunosuppressive domain are under preclinical evaluation. Paradoxically, ERV3-1-derived peptides are being investigated as cancer vaccine adjuvants to enhance antitumor immunity. Recent CRISPR screening identified ERV3-1 as a checkpoint in chimeric antigen receptor (CAR) T-cell therapies, with blockade strategies showing enhanced cytotoxicity in solid tumor models.

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Recombinant Human Endogenous retrovirus group 3 member 1 Env polyprotein (ERV3-1), partial