tetherin

Tetherin, also known as BST2 and CD317, is an interferon-inducible host restriction factor that inhibits the release of many enveloped viruses from infected cells by tethering virions to the plasma membrane.

In humans it is encoded by the BST2 gene and is expressed in a broad range of cell types, with expression upregulated by type I interferons during viral infection.

Protein structure: Tetherin is a type II membrane protein that contains an N-terminal cytoplasmic tail, a single transmembrane domain, an extracellular coiled-coil stalk, and a glycosylphosphatidylinositol (GPI) anchor at the C terminus. It forms disulfide-linked dimers and is glycosylated.

Mechanism: The combination of the transmembrane region and the GPI anchor allows tetherin to anchor budding virions to the cell surface, effectively inhibiting release of virions. Dimerization and the extracellular coiled-coil facilitate tethering, and the activity is enhanced by interferon-induced upregulation.

Viral countermeasures: The best characterized antagonist is HIV-1 Vpu, which reduces surface tetherin levels and promotes its removal from the plasma membrane, thereby restoring virion release. Other viruses have evolved distinct antagonists or strategies.

Impact: Tetherin is a key component of innate immunity against enveloped viruses and has been the subject of extensive research for its antiviral mechanism and potential therapeutic implications.