Human T-lymphotropic virus type 1 transmembrane glycoprotein gp21[1][2][5][7] (gp21[1][2][5][7])

The Human T-lymphotropic virus type 1 transmembrane glycoprotein gp21 is the transmembrane (TM) subunit of the HTLV-1 envelope glycoprotein, cleaved from the gp62 precursor alongside the surface (SU) subunit gp46 to form the functional Env trimer responsible for viral entry into host cells, primarily CD4+ T-cells.[1][2][5][7] Gp21 mediates membrane fusion through its N-terminal fusion peptide (FP), which inserts into the target cell membrane following receptor binding by gp46, enabling viral genome delivery; its structure features a trimeric coiled-coil domain, disulfide-bonded loop for chain reversal, and a C-terminal segment that anchors to the viral envelope.[2][5][7][8] Beyond fusion, gp21 harbors immunosuppressive activity, particularly via its FP, which inhibits antigen-specific T-cell activation downstream of the T-cell receptor complex, reducing Th1 cytokine production (e.g., IFN-γ, TNF-α) and transcription factors like T-bet while elevating Th2 responses (e.g., IL-4, IL-10, GATA3).[1][6] This modulation promotes viral persistence by evading antiviral immunity and has been shown to alleviate symptoms in T-cell hyperactivation models like experimental autoimmune encephalomyelitis, mimicking multiple sclerosis.[1] Structurally, gp21 exhibits evolutionary conservation in its coiled-coil and loop regions across retroviruses, contrasting with variable C-terminal elements that adapt to diverse surface subunits, highlighting its dual role in fusion and immune suppression.[2][3][8] No approved drugs directly target gp21, reflecting its status as a viral protein rather than a human therapeutic target.[1][2][5]

Other names

HTLV-1 gp21HTLV-1 TM (transmembrane subunit)