Bats Possess Unique Variants of the Antiviral Restriction Factor Tetherin

Joshua A. Hayward; Mary Tachedjian; Adam Johnson; Tamsin B. Gordon; Jie Cui; Glenn A. Marsh; Michelle L. Baker; Lin-Fa Wang; Gilda Tachedjian

In humans, tetherin is expressed across most cell types, including its BST-2 namesake bone marrow stromal cells, and expression may be upregulated by stimulation with type I interferons (28-30). Tetherin is a dimeric dual-anchor type II membrane protein that contains one protein anchor, a transmembrane domain near its N-terminus, an extracellular coiled-coil domain, and a glycophosphatidylinositol (GPI) lipid anchor, which is attached to its C-terminus as a post-translational modification (31) (32) (33) . Tetherin contains a number of conserved cytosine and asparagine motifs within the extracellular domain, with respective roles in dimerisation and glycosylation, and a dual-tyrosine motif Introduction (Y·x·Y) in its cytoplasmic region, which has a role in viral particle endocytosis and immune signaling cascades (25, 34) . Tetherin is located in lipid rafts at the plasma membrane where many viral particles bud during acquisition of their host membrane-derived viral envelopes (33) . During the viral budding process one anchor remains embedded in the nascent viral envelope while the other remains attached to the plasma membrane, tethering the virion to the cell and preventing its release into the extracellular environment (22, 32) .